Vision must infer the latent causes of retinal input from signals that are incomplete, noisy, and often ambiguous. This thesis asks whether primate vision is best understood as a predominantly feedforward computation or as a generative, recurrent process in which higher-order hypotheses help shape sensory representations over time. I propose that the visual brain is best described as performing analysis by synthesis: internal scene hypotheses generate predicted sensory structure, and perception emerges through iterative interactions between these predictions and incoming evidence.
\r\n\r\nThe first part of the thesis develops this proposal at the conceptual and neurobiological levels. Drawing on phenomena such as imagery, dreaming, active vision, bistable perception, perceptual completion, and the effects of prior knowledge, I argue that a purely feedforward account cannot fully explain the coordinated, context-sensitive, and inference-like nature of visual experience. I then review computational families of generative models and neuroscientific evidence for feedback, iterative dynamics, and laminar circuitry, proposing that these features are well suited to implement hypothesis-driven visual inference in the brain.
\r\n\r\nThe second part tests this framework in the macaque face-patch system using simultaneous Neuropixels recordings from face patches ML and AM. To ask whether degraded-face recognition engages feedback-supported inference, I measured the time at which degraded-face responses become aligned with intact identity representations. Under passive viewing of a wide range of degradations, both response timing and intact-to-degraded generalization followed the canonical posterior-to-anterior ordering, with ML preceding AM. Thus, degradation alone did not reveal an anterior-leading signature of top-down inference within inferotemporal cortex. In contrast, learning to associate ambiguous Mooney faces with their intact counterparts selectively reshaped ML population activity, increasing both representational separability and cross-condition generalization for upright Mooney faces. These findings suggest that top-down recruitment in the ventral stream is constrained and may depend not simply on degraded input, but on the availability of learned priors that can disambiguate it.
\r\n\r\nThe final part shows that high-level visual coding itself is dynamically reformatted over time. Large-scale recordings from ML and AM during viewing of faces and non-face objects revealed that face-selective neurons do not use a single, fixed encoding axis. Instead, responses to faces initially align with a domain-general object code, consistent with rapid face detection, but then undergo a rapid, concerted switch within 20 ms. This switch includes reversal of tuning in low dimensions of object space, emergence of new tuning in higher-dimensional face space, increased response sparsity, and improved reconstruction and discrimination of individual faces. The effect is stimulus-gated, appearing for faces but not for non-face objects, and resolves a long-standing debate by showing that inferotemporal face coding is both domain general and domain specific, but at different moments in time.
\r\n\r\nTogether, these studies support a view of primate vision as a dynamic and knowledge-sensitive process. Rather than relying on a static feedforward code alone, the visual system appears to use recurrent computations that allow sensory representations to be revised, sharpened, and reformatted as incoming evidence interacts with internal models and prior knowledge.
", "doi": "10.7907/v1xv-2152", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:18613", "collection": "thesis", "collection_id": "18613", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05232026-010040610", "type": "thesis", "title": "Neural Code for Dynamic Visual Experience in the Primate Brain", "author": [ { "family_name": "Lu", "given_name": "Jialiang", "orcid": "0000-0001-5403-3228", "clpid": "Lu-Jialiang" } ], "thesis_advisor": [ { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" }, { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Neuroscience increasingly needs experimental tools that can study vision in naturalistic, continuous, and interactive scenes. This thesis presents a methodological and scientific framework for studying naturalistic vision and social scene representation in the primate brain. I developed MINOS, a Unity-based platform that integrates complex stimulus generation, behavioral control, hardware communication, synchronization, and analysis-ready data recording in one modular environment. I also developed a compact piezo-actuated Neuropixels insertion system for acute large-scale electrophysiology in awake macaques, designed to support precise, reproducible, and flexible multi-probe recordings in limited chamber space. Using these tools, I recorded neural populations from inferotemporal cortex and ventrolateral prefrontal cortex while a monkey freely viewed a continuous social scene in which one or two characters entered, waited, interacted, and left. This design kept precise event labels while reducing the strong visual transients of discrete image presentation. The results showed a clear functional difference between the two regions. Inferotemporal cortex mainly represented the currently fixated face and updated rapidly after fixation changes. Ventrolateral prefrontal cortex integrated information across time and scene state, represented current and recently relevant identities, encoded entering and leaving events, and maintained identity information in different low-dimensional formats depending on whether a person was fixated or not. It also carried a stable and largely identity-independent code for action category and action role across sessions. Together, these findings suggest that prefrontal cortex helps organize dynamic social scenes by combining context-dependent identity representations with a more general relational code. This thesis therefore contributes new experimental tools for primate systems neuroscience and opens a route for studying how the brain represents structured events during continuous visual experience.", "doi": "10.7907/3ewf-6795", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:16520", "collection": "thesis", "collection_id": "16520", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06122024-185146643", "primary_object_url": { "basename": "hcourellis_dissertation_June_2025.pdf", "content": "final", "filesize": 9004085, "license": "other", "mime_type": "application/pdf", "url": "/16520/1/hcourellis_dissertation_June_2025.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "A Study on the Content, Format, and Implementation of Neural Representations That Underlie Flexible Human Cognition", "author": [ { "family_name": "Courellis", "given_name": "Hristos Spiridonos", "orcid": "0000-0001-5963-679X", "clpid": "Courellis-Hristos-Spiridonos" } ], "thesis_advisor": [ { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" } ], "thesis_committee": [ { "family_name": "Andersen", "given_name": "Richard A.", "orcid": "0000-0002-7947-0472", "clpid": "Andersen-R-A" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Humans are the most capable cognitive generalists to walk the earth. They have a remarkable capacity for flexibility reallocating cognitive resources to rapidly acquire and execute an effectively infinite number of tasks. By utilizing the opportunity to record single-neuron activity in the frontal and temporal lobes of awake, behaving neurosurgical patients, we aim to elucidate the principles by which task representations are organized at the neural-circuit level to give rise to flexible cognition and behavior.
\r\n\r\nOur research program consists of four inter-related projects, each of which seeks to clarify the content, format, and single-neuron implementation of the representations that underlie different aspects of cognition and behavior that are uniquely human. In the first project, we demonstrate that the emergence of disentangled task representations in the hippocampus correlate with the ability of an individual to discover and perform inference on the state of latent context variables in their environment. In the second project, we describe differences in the temporal stability of instructed task representations in the hippocampus and medial frontal cortex, and show that they rely on persistent activity of single-neurons that lasts for 1-2 orders of magnitude longer than is typically studied in working-memory tasks. In the third project, we study the neural mechanisms of task-switching costs, and show that the state of medial frontal cortical context-representing neurons immediately following instructions is predictive of switching cost. In the fourth project, we evaluate the extent to which frontal cortical task representations inherit the compositional structure of natural language, and attempt to predict the neural representation of novel tasks as patients perform zero-shot generalization in a large task space.
\r\n\r\nTogether, these projects constitute a first step in understanding the neural computations that underlie cognitive processing used by humans to solve complex, multi-task environments.
", "doi": "10.7907/edk1-kb22", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16191", "collection": "thesis", "collection_id": "16191", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09272023-165737414", "primary_object_url": { "basename": "WadiaThesis_Full_Final.pdf", "content": "final", "filesize": 10017145, "license": "other", "mime_type": "application/pdf", "url": "/16191/1/WadiaThesis_Full_Final.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "How We Imagine: Insights from Single Neuron Recordings in the Human Brain", "author": [ { "family_name": "Wadia", "given_name": "Varun Spenta", "orcid": "0009-0009-5401-5367", "clpid": "Wadia-Varun-Spenta" } ], "thesis_advisor": [ { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" }, { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "As human beings interact with the world, we sample it, build representations of its underlying structure, and subsequently use that knowledge for future reasoning - also called modeling the world. This model is generative, allowing our knowledge of the world to influence our perception and in extreme cases induce perception in the absence of any external stimulus. This phenomenon called mental imagery is a remarkable cognitive ability that allows us to remember previous experiences, imagine new ones, make plans, and solve problems. In the visual domain, our ability to generate visual percepts without external stimulation is the basis of our memory for experiences, as episodic memories are simply a subset of all possible experiences we could imagine. Animal studies have yielded rich insight into bottom-up visual processing, from the first discovery of neurons that respond to complex objects like faces to determining the precise code for general objects in macaque inferotemporal (IT) cortex. However, the neural mechanisms of internally generated top-down processing have been much more elusive. Here we present findings on the mechanisms of visual imagery at single neuron resolution. We approached deciphering visual imagery by first laying out coding principles for object perception and then directly comparing responses during viewing to subsequent imagery of those images. We recorded 384 visually responsive neurons in inferotemporal (IT) cortex of 12 epilepsy patients as they viewed and subsequently imagined carefully parametrized visual objects. We verified that neurons in IT cortex are \u2018axis tuned\u2019, i.e. as in macaques they represent visual objects by encoding specific axes that span a high dimensional object feature space. 218/384 visually responsive neurons (~58%) were axis tuned, and the axis model explained more variance than other models tested. Armed with this code for visual objects we examined neural responses during pure imagery in the same neurons. We demonstrate robust reactivation of individual neurons across the brain (~35% of neurons across the brain and ~50% of neurons in IT cortex) and a recapitulation of viewing stimulus preference during pure visual imagery in IT. By first uncovering the code for visual objects and examining it during imagery, we demonstrate that neurons in IT cortex subserve visual imagery by reinstating visual context. This study marks the first detailed exploration of visual perception and imagery in the human brain.", "doi": "10.7907/8nw5-1q14", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:15039", "collection": "thesis", "collection_id": "15039", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10112022-213905012", "primary_object_url": { "basename": "Caltech_Thesis_Yu_Li_Ni_20221019.pdf", "content": "final", "filesize": 6497485, "license": "other", "mime_type": "application/pdf", "url": "/15039/1/Caltech_Thesis_Yu_Li_Ni_20221019.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Developing Tools for Neurobiology: The Retina as a\u00a0Neuropharmacology Testbed & Electrode Pooling\u00a0to Boost Extracellular Array Recording", "author": [ { "family_name": "Ni", "given_name": "Yu-Li", "orcid": "0000-0003-1600-9854", "clpid": "Ni-Yu-Li" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Lois", "given_name": "Carlos", "orcid": "0000-0002-7305-2317", "clpid": "Lois-Carlos" }, { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "This thesis presents two tool development projects for neurobiology and one explorative project to find organizing principles for autism.
\r\n\r\nThe first project (Chap 2, Retina as Probe) was conceived to tackle the problem that there hasn\u2019t been a reliable model system for system-level neuropharmacology. We introduce a testbed for this: the mammalian retina. The retina involves many of the known neurotransmitters and modulators. Yet its synaptic wiring is well understood, and quantitative models exist to explain its input-output functions. One can connect the systems-level effects to the underlying cellular and molecular causes. To demonstrate the retina\u2019s use, we explored the effects of a range of general anesthetics on the light responses of the mouse retina. At sub-anesthetic doses, we found that certain anesthetics exert a paradoxical effect: they increase the light response of some retinal neurons and suppress the response of others. Notably, this occurred for alcohols and ketamine but not for isoflurane. We traced these effects to transmitter release at a specific synapse and, in one case, to a specific presynaptic ion channel. All the anesthetics silenced the output of the retina completely at concentrations similar to their effective dose for anesthesia in humans. Sedatives reduced retinal sensitivity but did not silence it. Finally, we used specific drugs that target hypothesized molecular mechanisms to probe how much they each contribute to anesthesia of the retina.
\r\n\r\nThe second project which attempted to probe the principles of autism (Chap 3) was conceptually a direct extension of the retina as a testbed. Similar to the situation in seeking for what the mechanism of general anesthesia is, the field of autism research also lacks a good testbed but for systemically comparing gene mutation - circuit defect - behavior outcomes. Similarly, we utilized the retina as a platform to identify circuit defects in four different autism model mice and followed through the different mouse line\u2019s behavior readouts using our lab\u2019s maze navigation paradigm. We discovered that the different autism mouse lines varied in the retinal circuits and varied in their navigation preferences. Nevertheless, unlike the anesthetic project, there wasn\u2019t a simple mechanism to explain why or how these differences are coupled together.
\r\n\r\nThe last project, Electrode Pooling, (Chap 4) aimed to boost the yield of extracellular recording electrode arrays with a novel method we named electrode pooling. The per-implant yield of extracellular recording leaped significantly from the order of tens to the order of hundreds when engineers built multiple electrode arrays based on silicon technology to replace tetrode wires. Unfortunately, this yield-per-site is already maxed out with modern silicon technology. The constraint of the yield is mainly biological, as explained in the chapter, and thus could not be further advanced by improving the manufacturing processes of semiconductors. Our solution utilized an approach that multiplexed the array recording sites (not the bottleneck) onto the readout wires with accompanying filters (the actual bottleneck). Specifically, the method proposes intelligently choosing many recording sites that carry signals and connecting them to a single wire via manipulating the switches and later un-mixed with a spike-sorting algorithm. We demonstrated the first proof-of-principle study that shows that one could get more single-neuron recordings per implant site with electrode pooling, and made recommendations on the hardware design that could facilitate the advancement of probes that use pooling algorithms.
", "doi": "10.7907/jeh6-w316", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15041", "collection": "thesis", "collection_id": "15041", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10132022-000100592", "primary_object_url": { "basename": "bernstein_thesis.pdf", "content": "final", "filesize": 2113002, "license": "other", "mime_type": "application/pdf", "url": "/15041/1/bernstein_thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Optimisation & Generalisation in Networks of Neurons", "author": [ { "family_name": "Bernstein", "given_name": "Jeremy David", "orcid": "0000-0001-9110-7476", "clpid": "Bernstein-Jeremy-David" } ], "thesis_advisor": [ { "family_name": "Yue", "given_name": "Yisong", "orcid": "0000-0001-9127-1989", "clpid": "Yue-Yisong" } ], "thesis_committee": [ { "family_name": "Tropp", "given_name": "Joel A.", "orcid": "0000-0003-1024-1791", "clpid": "Tropp-J-A" }, { "family_name": "Liu", "given_name": "Ming-Yu", "orcid": "0000-0002-2951-2398", "clpid": "Liu-Ming-Yu" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Yue", "given_name": "Yisong", "orcid": "0000-0001-9127-1989", "clpid": "Yue-Yisong" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The goal of this thesis is to develop the optimisation and generalisation theoretic foundations of learning in artificial neural networks. The thesis tackles two central questions. Given training data and a network architecture:
\r\n\r\nOn optimisation, an essential feature of neural network training is that the network weights affect the loss function only indirectly through their appearance in the network architecture. This thesis proposes a three-step framework for deriving novel \u201carchitecture aware\u201d optimisation algorithms. The first step\u2014termed functional majorisation\u2014is to majorise a series expansion of the loss function in terms of functional perturbations. The second step is to derive architectural perturbation bounds that relate the size of functional perturbations to the size of weight perturbations. The third step is to substitute these architectural perturbation bounds into the functional majorisation of the loss and to obtain an optimisation algorithm via minimisation. This constitutes an application of the majorise-minimise meta-algorithm to neural networks.
\r\n\r\nOn generalisation, a promising recent line of work has applied PAC-Bayes theory to derive non-vacuous generalisation guarantees for neural networks. Since these guarantees control the average risk of ensembles of networks, they do not address which individual network should generalise best. To close this gap, the thesis rekindles an old idea from the kernels literature: the Bayes point machine. A Bayes point machine is a single classifier that approximates the aggregate prediction of an ensemble of classifiers. Since aggregation reduces the variance of ensemble predictions, Bayes point machines tend to generalise better than other ensemble members. The thesis shows that the space of neural networks consistent with a training set concentrates on a Bayes point machine if both the network width and normalised margin are sent to infinity. This motivates the practice of returning a wide network of large normalised margin.
\r\n\r\nPotential applications of these ideas include novel methods for uncertainty quantification, more efficient numerical representations for neural hardware, and optimisers that transfer hyperparameters across learning problems.
", "doi": "10.7907/1jz8-5t85", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15130", "collection": "thesis", "collection_id": "15130", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04092023-200347393", "primary_object_url": { "basename": "Thesis_Charles-Guan.pdf", "content": "final", "filesize": 9022504, "license": "other", "mime_type": "application/pdf", "url": "/15130/2/Thesis_Charles-Guan.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Neural Coding of Finger Movements in Human Posterior Parietal Cortex and Motor Cortex", "author": [ { "family_name": "Guan", "given_name": "Charles", "orcid": "0000-0002-8040-8844", "clpid": "Guan-Charles" } ], "thesis_advisor": [ { "family_name": "Andersen", "given_name": "Richard A.", "orcid": "0000-0002-7947-0472", "clpid": "Andersen-R-A" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" }, { "family_name": "Yue", "given_name": "Yisong", "orcid": "0000-0001-9127-1989", "clpid": "Yue-Yisong" }, { "family_name": "Andersen", "given_name": "Richard A.", "orcid": "0000-0002-7947-0472", "clpid": "Andersen-R-A" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "We use our hands constantly in our everyday lives. This seemingly simple ability is disrupted in individuals with cervical spinal cord injuries. By circumventing injured signal pathways, brain-computer interfaces (BCIs) promise to enable such individuals to control artificial limbs for everyday use. However, existing BCI limb control remains coarse and inflexible, because we do not understand how the recorded neural activity relates to dexterous movement. As a result, BCI control in physical settings remains frustratingly difficult for paralyzed users. To improve dexterous BCI control, I studied the neural coding of individual finger movements in the posterior parietal cortex and motor cortex of tetraplegic participants. These regions are directly involved in dexterous hand movements and are candidates for BCI recording implants. Finger coding matched the correlation structure and dynamics of able-bodied usage, reflecting preserved motor circuits even after paralysis. Individual finger movements of each hand were coded in a factorized, correlated manner that still allowed decoding. Participants controlled artificial fingers with state-of-the-art accuracy. Finally, we studied the temporal dynamics of neural control to understand how existing models of neural activity extend to BCI control. These findings contribute to the understanding of human hand movements and advance the development of dexterous BCIs.", "doi": "10.7907/31rt-cy14", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:16061", "collection": "thesis", "collection_id": "16061", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06022023-192547723", "primary_object_url": { "basename": "ShengThesis_CaltechTHESIS.pdf", "content": "final", "filesize": 8747307, "license": "other", "mime_type": "application/pdf", "url": "/16061/1/ShengThesis_CaltechTHESIS.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Synthetic Circuits for Multicellular Spatial Patterning", "author": [ { "family_name": "Wang", "given_name": "Sheng", "orcid": "0000-0002-4070-7313", "clpid": "Wang-Sheng" } ], "thesis_advisor": [ { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" } ], "thesis_committee": [ { "family_name": "Goentoro", "given_name": "Lea A.", "orcid": "0000-0002-3904-0195", "clpid": "Goentoro-L-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Self-organized spatial periodic patterning mechanisms are responsible for the generation of repetitive structures, such as digits, vertebrae, and teeth, during multicellular development. Adopting a synthetic biology approach, we aim to unravel the core principles of multicellular spatial patterning by designing and reconstituting it in tissue-cultured cell lines.
\r\n\r\nThe reaction-diffusion mechanism, as an established paradigm, has successfully elucidated and forecasted pattern formation across varying scales and species. However, the potential for reconstituting synthetic reaction-diffusion patterns using unconventional reaction-diffusion elements within mammalian cell cultures has been insufficiently explored, thus leaving a gap in our comprehension of how spatial periodic patterns could be generated.
\r\n\r\nThe simplest reaction-diffusion systems are thought to necessitate a minimum of two morphogens to generate periodic patterns. In contrast, with the help of mathematical modeling, we illustrate that a simpler circuit, comprising only a single diffusible morphogen, can adequately produce long-range, spatially periodic patterns. These patterns propagate outward from transient initiating perturbations and remain stable after the disturbance is removed. Moreover, introducing an additional bistable intracellular feedback or operation on a growing cell lattice can enhance the robustness of the patterning against noise.
\r\n\r\nConcurrently, we reconstruct the Turing pattern in mammalian cell culture utilizing a bottom-up approach. We construct a synthetic circuit based on two signaling pathways. After validation of each circuit component, we exhibit the spatial pattern formation driven by a synthetic reaction-diffusion circuit within the mammalian cell line. This adaptable circuit facilitates us to adjust circuit parameters or implement various boundary conditions, thereby revealing the impact of these alterations on patterning dynamics.
\r\n\r\nCollectively, these findings lay the groundwork for the engineering of pattern formation in the nascent field of synthetic developmental biology.
", "doi": "10.7907/3rbk-g805", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:14639", "collection": "thesis", "collection_id": "14639", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272022-181044242", "primary_object_url": { "basename": "Yanting_Han_2022_Thesis.pdf", "content": "final", "filesize": 127719549, "license": "other", "mime_type": "application/pdf", "url": "/14639/1/Yanting_Han_2022_Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Emotion Experience from Stories, Videos and Everyday Life: Structure and Individual Differences", "author": [ { "family_name": "Han", "given_name": "Yanting", "orcid": "0000-0003-3381-2059", "clpid": "Han-Yanting" } ], "thesis_advisor": [ { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Eberhardt", "given_name": "Frederick D.", "clpid": "Eberhardt-F-D" }, { "family_name": "Shimojo", "given_name": "Shinsuke", "orcid": "0000-0002-1290-5232", "clpid": "Shimojo-S" }, { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" } ], "local_group": [ { "literal": "COVID-19" }, { "literal": "div_bbe" } ], "abstract": "Most studies of emotion have as their subject matter the emotion experiences that people can describe and rate. By contrast to this approach from psychology, studies in animals, and some biological studies in humans, focus on behavior and its adaptive function. These two literatures typically use very different corresponding features by which to characterize emotion: categories or dimensions describing feelings for which we have convenient words, for the former (e.g., happiness, pleasantness), and functional properties for the latter (e.g., persistence, generalizability, approachabil- ity). In this thesis I use both sets of ratings, and I ask whether the latter, biologically inspired features could also be used to characterize people\u2019s emotion experiences, and might reveal novel dimensions of variability. They also typically use different sets of stimuli to induce the emotions: lexical stimuli in which participants are asked to imagine something hypothetical are common in human studies; ecologically valid stimuli that at least the subjects cannot distinguish from the real world are common in animal studies. Here I used three domains of stimuli: stories, videos, and real-life experiences, in the same set of participants, permitting a unique comparison.
\r\n\r\nI took advantage of a sample of approximately 1000 Americans who were surveyed longitudinally over the internet during the COVID-19 pandemic. I collected ratings of emotion experiences evoked by three classes of stimuli: a validated set of short stories, a validated set of short videos, and actual experiences in real life across multiple waves. I found that all three types of emotion experiences could be characterized by low dimensional spaces, with the first two factors that accounted for most of the variance in people\u2019s ratings corresponding to the dimensions of valence and arousal, in line with prior work. However, I discovered additional novel factors related to generalizability (the extent to which an emotion experience is shared across many different situations and occurrences) or modularity (the extent to which an emotion experience is unique to specific situations). The findings show that emotion features not usually assessed in humans can be recovered from subjective ratings of their experiences. I argue for a revision of current dimensional theories of emotion: they have been incomplete because they were restricted to ratings entrenched in how we think of our conscious experience, and the typical English words we use to describe it. The new dimensions validate some theories of emotion and offer hope for linking psychological studies in humans with behavioral or neurobiological work across species. I also characterized the distributions of the three types of emotion experiences and found that emotions were distributed along continuous gradients, with no well-separated clusters even for emotions belonging to the six basic emotion categories.
\r\n\r\nMy thesis presents two additional topics that capitalize on my unique sample: the emotions experienced during the COVID pandemic, and individual differences. For example, I also found that resilience buffered individuals against the effect of loneliness on depression, and that people who had tested positive for COVID felt more morally disgusted towards acts of violating social norms. I also explored the association between psychological traits and differences in emotion experiences both in terms of the magnitudes of the ratings and the overall correlation structure across scales. Again, the richness of my dataset reveals a number of associations that are theoretically interesting and that will be of relevance to understanding mood and anxiety disorders as well.
\r\n\r\nAll of the data will be made publicly available, and the core parts of many of the investigations were pre-registered.
", "doi": "10.7907/yhmt-9t69", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14449", "collection": "thesis", "collection_id": "14449", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12152021-005204320", "type": "thesis", "title": "Biological Intelligence: from Behavior to Learning Theory", "author": [ { "family_name": "Zhang", "given_name": "Tony (Haoyu)", "orcid": "0000-0002-5198-499X", "clpid": "Zhang-Tony-Haoyu" } ], "thesis_advisor": [ { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" } ], "thesis_committee": [ { "family_name": "Yue", "given_name": "Yisong", "orcid": "0000-0001-9127-1989", "clpid": "Yue-Yisong" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Bouman", "given_name": "Katherine L.", "orcid": "0000-0003-0077-4367", "clpid": "Bouman-K-L" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Knowing how to learn, think, and act is not just a hallmark of intelligence, but a necessity of survival for many organisms. Behavior, the complete set of actions of species, allows us to glimpse into the minds of humans and animals, and by extension, intelligence itself. Biological intelligence is characterized by fast adaptation to changes and challenges, which is what allows species to survive in natural environments from starvation and predation. To study learning in a controlled setting, we can observe the behavior evoked through decision-making tasks that make it possible to quantify and analyze learning. By modeling the extracted behavioral features, we could start to understand the possible underlying mechanisms by proposing neural theory models, and look for those signals in the brain. Understanding the neural mechanisms of learning also strengthens the basis for building intelligent machines that are flexible and adaptive to the nonstationary world we live in. In this thesis, I present works in (1) automating behavioral setups and modeling suboptimal behavior in a traditional decision-making task, (2) using an ethological navigation task to characterize fast-sequence learning, and (3) how neural theory can explain some core behavioral phenomena in (2), and be used to solve a central problem in graph search.
", "doi": "10.7907/8z4q-8g15", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14597", "collection": "thesis", "collection_id": "14597", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05232022-073842501", "primary_object_url": { "basename": "Yang_Thesis_2022.pdf", "content": "final", "filesize": 14247032, "license": "other", "mime_type": "application/pdf", "url": "/14597/1/Yang_Thesis_2022.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Transformations and Functions of Neural Representations in a Subcortical Social Behavior Network", "author": [ { "family_name": "Yang", "given_name": "Bin", "orcid": "0000-0002-3878-1530", "clpid": "Yang-Bin" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Oka", "given_name": "Yuki", "orcid": "0000-0003-2686-0677", "clpid": "Oka-Yuki" }, { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The brain functions by processing sensory information such as vision, smell, and touch, integrating it with internal states (hunger, fear, aggression) and memory to produce relevant motor outputs (eating, fleeing, or fighting). To understand the brain, neuroscientists study neural representations (patterns of neural activity that correlate with features of the outside world) to and perform perturbations (activate or silence groups of neurons) to determine its function. Past studies on neural representations gave us insights into how sensory regions filter complex inputs to retain relevant information and how coordinated activity in the motor regions produce complex motor actions. However, little is known about how information is processed in the inner brain (between sensory and motor) and how behaviors are controlled. Mating and aggression are innate social behaviors that are essential for animals\u2019 survival. During social interactions, such as those preceding mating or fighting, the brain must determine the sex of a conspecific to produce sex-appropriate behaviors that are conducive to its survival. Functional studies demonstrated that they are controlled by deep subcortical circuits in the extended amygdala and hypothalamus. My thesis attempts to understand how the inner brain works by 1) showing that chemosensory cues encoding conspecific\u2019s sex are transformed to neural representations of mating and aggression during social interactions by recording from a genetically defined group of neurons in different regions of the extended amygdala and hypothalamus. 2) Demonstrating that the neural activity representing conspecific\u2019s sex is necessary for the emergence of behavioral representations in the hypothalamus.
", "doi": "10.7907/v13r-yt57", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14955", "collection": "thesis", "collection_id": "14955", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06072022-184731596", "type": "thesis", "title": "Innate Navigation: Magnetic Sensation and Maze Learning", "author": [ { "family_name": "Rosenberg", "given_name": "Matthew Hutson", "orcid": "0000-0002-6728-915", "clpid": "Rosenberg-Matthew- Hutson" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" }, { "family_name": "Siapas", "given_name": "Athanassios G.", "orcid": "0000-0001-8837-678X", "clpid": "Siapas-A-G" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "This thesis aims to advance the understanding of the neurobiology of navigation through the investigation of two topics: magnetic sensation and maze navigation. The central question of this work may be framed as follows: how do animals find their way to key resources that are necessary for survival? Three projects are presented to address this.
\r\n\r\nChapter II explores a sensory hypothesis that some animals may navigate long distances by directly sensing the earth\u2019s magnetic field. Awake zebra finches were stimulated with magnetic fields that varied sinusoidally in time while electrical recordings were collected via multi-channel electrodes. Preliminary negative results are presented, along with a detailed statistical treatment indicating no significant effect of magnetic stimulation on neural activity.
\r\n\r\nChapter III presents a novel approach to studying learning and navigation in animal subjects. Mice are allowed free passage between a normal home cage and a complex maze environment, coming and going as they please. Sated animals, with free access to food and water, spend significant portions of a given multi-hour experiment in the maze and display efficient exploration. Water-restricted animals show three additional phenomena: immediate knowledge of the route home, rapid learning of the location of a single water port among 64 similar locations, and a moment of \"sudden insight\" in which the rate at which long, direct routes to the water source, beginning from many locations, increases discontinuously.
\r\n\r\nChapter IV offers a simple, biologically feasible circuit model that recapitulates and explains some of the rapid learning behaviors we observe in mice. This model suggests a mechanism that might allow mice to flexibly store and recall direct routes to different resources that are activated by different internal drives.
\r\n\r\nThe final chapter outlines some potential directions for future inquiry, including potential maze experiments to conduct with wireless electrophysiology and expansion of the range of species tested for magnetic perception. The Appendix briefly describes some follow-up experiments and intriguing preliminary results. Similarities in the navigation deficit displayed by mice that have been experimentally perturbed in several disparate ways is noted briefly. These perturbations include whisker trimming, olfactory neuron ablation, genetic ablation of cortex and hippocampus, and opiate intoxication.
", "doi": "10.7907/hmyr-3d58", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14170", "collection": "thesis", "collection_id": "14170", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05222021-190729800", "type": "thesis", "title": "Neural Control of Male and Female Aggression in Drosophila", "author": [ { "family_name": "Chiu", "given_name": "Hui", "orcid": "0000-0002-1820-8411", "clpid": "Chiu-Hui" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Aggression is essential for an individual\u2019s survival, but it can also lead to unfavorable consequences when misregulated. It is thus important to study the neural basis of this behavior not only for learning how the nervous system is constructed to generate an innate behavior but also for finding the causality of misregulation. Although many circuit and molecular mechanisms underlying aggression have been revealed, our knowledge is mostly restricted to males. Given that sexual differences in aggression are seen in most if not all species, the mechanisms that we learned in one sex may not be directly applied to the other. Therefore, studying the neural basis of aggression in both sexes is necessary for gaining a full understanding of this behavior. Drosophila serves as a unique model for such studies because males and females differ not only in the level of aggressiveness but also in the motor patterns. Interestingly, the aggression-promoting neurons that have been identified so far are mostly sex-specific, raising the possibility that males and females adopt distinct circuits for controlling aggression. However, many sexually shared features of aggression also imply the existence of common circuit elements. My thesis work investigated whether any aggression circuit modules are shared by the two sexes and how the circuit is organized to generate sexually shared and dimorphic motor patterns. Through a behavioral screen and the genetic intersection approach, we identified a pair of sexually shared neurons, CAP, that regulates aggressive approach in both sexes, as well as a pair of male-specific neurons, MAP, whose activation promotes the transition from approach to male-specific attack. We subsequently identified the female homologue, fpC1 neurons, whose activation induces female aggression. Supported by the in vivo imaging and the behavioral epistasis results, we confirmed the functional connectivity between CAP and MAP/fpC1 in males and females, respectively. Lastly, we showed that the connectivity between CAP and MAP/fpC1 is strengthened in socially isolated flies, which exemplifies how circuits can be modified by social isolation to enhance aggression in both sexes. The connectivity between CAP and MAP/fpC1 provides a circuit logic for the control of sexually shared and dimorphic aggressive behaviors. It can be used as an entry point for circuit mapping as well as for further investigation of mechanisms underlying sexual differences in aggression.
", "doi": "10.7907/9rf6-5727", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14192", "collection": "thesis", "collection_id": "14192", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05282021-174607976", "primary_object_url": { "basename": "bagherian_dawna_2021.pdf", "content": "final", "filesize": 8166683, "license": "other", "mime_type": "application/pdf", "url": "/14192/3/bagherian_dawna_2021.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Artificial Neural Networks for Nonlinear System Identification of Neuronal Microcircuits", "author": [ { "family_name": "Bagherian", "given_name": "Dawna Paria", "orcid": "0000-0003-4465-552X", "clpid": "Bagherian-Dawna-Paria" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Yue", "given_name": "Yisong", "orcid": "0000-0001-9127-1989", "clpid": "Yue-Yisong" }, { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "This thesis explores the application of artificial neural networks (ANNs) to nonlinear system identification. We use neuronal microcircuits in the retina as a testbed for our technique, which relies upon the marriage of partial anatomical information with large electrophysiological datasets. Rather than a typical application of machine learning, our primary goal is not to predict the output of retinal circuits, but rather to uncover their structure. We begin with a theoretical exploration in a toy problem and provide a proof of unique identifiability under a specific set of conditions. We then perform empirical simulations in a number of different circuit architectures and explore the space of constraints and regularizers to demonstrate that this technique is feasible in a hyperparametric regime that lends itself well to neuroscience datasets. We then apply the technique to mouse retinal datasets and show that we can both recover known biological information as well as discover new hypotheses for biological exploration. We end with an exploration of active stimulus design algorithms to distinguish between circuit hypotheses.
", "doi": "10.7907/rj2p-8g11", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14263", "collection": "thesis", "collection_id": "14263", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06082021-032229529", "type": "thesis", "title": "Life Without Cortex: Subcortical Circuits in Naturalistic Behaviors", "author": [ { "family_name": "Turan", "given_name": "Zeynep", "orcid": "0000-0003-0704-5116", "clpid": "Turan-Zeynep" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" }, { "family_name": "Lois", "given_name": "Carlos", "orcid": "0000-0002-7305-2317", "clpid": "Lois-Carlos" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "A major goal of neuroscience is to understand the neural circuits underlying animal behavior. Many contemporary studies focus on behavioral tasks which do not reflect realistic conditions, such as mapping an arbitrary sensory stimulus to motor output. Given that the brain evolved within the context of the natural environment, it is more likely that these circuits were optimized for naturalistic behaviors such as avoiding predators, hunting, and social interactions with conspecifics. Many of these naturalistic behaviors predate the great expansion of the neocortex in mammals, as they are crucial for the survival of any animal. Using a mutant mouse model and surgical techniques, we show that the evolutionarily ancient subcortical circuits of mice are sufficient for sensory processing, stimulus discrimination, and exhibiting robust innate defensive behaviors in a predator avoidance assay. Furthermore, these animals are capable of navigating a complex labyrinth, which challenges long-held beliefs that learning and memory require the neocortex and the hippocampus. Our results emphasize the significant capacity of subcortical circuits in behaviors necessary for survival and illustrate the importance of using naturalistic behaviors to probe brain function.", "doi": "10.7907/czd1-dp02", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14170", "collection": "thesis", "collection_id": "14170", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05222021-190729800", "type": "thesis", "title": "Neural Control of Male and Female Aggression in Drosophila", "author": [ { "family_name": "Chiu", "given_name": "Hui", "orcid": "0000-0002-1820-8411", "clpid": "Chiu-Hui" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Aggression is essential for an individual\u2019s survival, but it can also lead to unfavorable consequences when misregulated. It is thus important to study the neural basis of this behavior not only for learning how the nervous system is constructed to generate an innate behavior but also for finding the causality of misregulation. Although many circuit and molecular mechanisms underlying aggression have been revealed, our knowledge is mostly restricted to males. Given that sexual differences in aggression are seen in most if not all species, the mechanisms that we learned in one sex may not be directly applied to the other. Therefore, studying the neural basis of aggression in both sexes is necessary for gaining a full understanding of this behavior. Drosophila serves as a unique model for such studies because males and females differ not only in the level of aggressiveness but also in the motor patterns. Interestingly, the aggression-promoting neurons that have been identified so far are mostly sex-specific, raising the possibility that males and females adopt distinct circuits for controlling aggression. However, many sexually shared features of aggression also imply the existence of common circuit elements. My thesis work investigated whether any aggression circuit modules are shared by the two sexes and how the circuit is organized to generate sexually shared and dimorphic motor patterns. Through a behavioral screen and the genetic intersection approach, we identified a pair of sexually shared neurons, CAP, that regulates aggressive approach in both sexes, as well as a pair of male-specific neurons, MAP, whose activation promotes the transition from approach to male-specific attack. We subsequently identified the female homologue, fpC1 neurons, whose activation induces female aggression. Supported by the in vivo imaging and the behavioral epistasis results, we confirmed the functional connectivity between CAP and MAP/fpC1 in males and females, respectively. Lastly, we showed that the connectivity between CAP and MAP/fpC1 is strengthened in socially isolated flies, which exemplifies how circuits can be modified by social isolation to enhance aggression in both sexes. The connectivity between CAP and MAP/fpC1 provides a circuit logic for the control of sexually shared and dimorphic aggressive behaviors. It can be used as an entry point for circuit mapping as well as for further investigation of mechanisms underlying sexual differences in aggression.
", "doi": "10.7907/9rf6-5727", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:11809", "collection": "thesis", "collection_id": "11809", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10072019-141728052", "primary_object_url": { "basename": "Davis_HunterC_2019_final.pdf", "content": "final", "filesize": 4540297, "license": "other", "mime_type": "application/pdf", "url": "/11809/1/Davis_HunterC_2019_final.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Mechanistic Insights for Magnetic Imaging and Control of Cellular Function", "author": [ { "family_name": "Davis", "given_name": "Hunter Cole Davis", "orcid": "0000-0003-1655-692X", "clpid": "Davis-Hunter-Cole-Davis" } ], "thesis_advisor": [ { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "thesis_committee": [ { "family_name": "Miller", "given_name": "Thomas F.", "orcid": "0000-0002-1882-5380", "clpid": "Miller-T-F" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Cushing", "given_name": "Scott K.", "orcid": "0000-0003-3538-2259", "clpid": "Cushing-Scott-K" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The vast biomolecular toolkit for optical imaging and control of cellular function has revolutionized the study of in vitro samples and superficial tissues in living organisms but leaves deep tissue unexplored. To look deeper in tissue and observe system-level biological function in large organisms requires a modality that exploits a more penetrant form of energy than visible light. Magnetic imaging with MRI reveals the previously unseen, with endogenous tissue contrast and practically infinite penetration depth. While these clear advantages have made MRI a cornerstone of modern medical imaging, the sparse library of molecular agents for MRI have severely limited its utility for studies of cellular function in vivo. The development of new molecular agents for MRI has suffered from a lack of tools to study the connection between changes in the microscale cellular environment and the corresponding millimeter-scale MRI contrast. Bridging this gap requires revisiting the mechanistic underpinnings of MRI contrast, casting aside some of the simplifications that smooth over sub-voxel heterogeneity that is rich with information pertinent to the underlying cell state.
\r\n\r\nHere, we will demonstrate theoretical, computational, and experimental connections between subtle changes in microscale cellular environment and resultant MRI contrast. After reviewing some foundational principles of MRI physics in the first chapter, the second chapter of the thesis will explore computational models that have significantly enhanced the development of genetically encoded agents for MRI, including the first genetically encoded contrast agent for diffusion weighted imaging. By improving the efficacy of these genetically encoded agents, we unlock MRI reporter genes for in vivo studies of cellular dynamics much in the same way that the engineering of Green Fluorescent Protein has dramatically improved in vitro studies of cellular function.
\r\n\r\nIn the third chapter, we introduce our study that maps microscale magnetic fields in cells and tissues and connects those magnetic fields to MRI contrast. Such a connection has previously been experimentally intractable due to the lack of methods to resolve small magnetic perturbations with microscale resolution. To overcome this challenge, we leverage nitrogen vacancy diamond magnetometry to optically probe magnetic fields in cells with sub-micron resolution and nanotesla sensitivity, together with iterative localization of field sources and Monte Carlo simulation of nuclear spins to predict the corresponding MRI contrast. We demonstrate the utility of this technology in an in vitro model of macrophage iron uptake and histological samples from a mouse model of hepatic iron overload. In addition, we show that this technique can follow dynamic changes in the magnetic field occurring during contrast agent endocytosis by living cells. This approach bridges a fundamental gap between an MRI voxel and its microscopic constituents and provides a new capability for noninvasive imaging of opaque tissues.
\r\n\r\nIn the fourth chapter, we focus on the use of magnetic fields to perturb, rather than image, biological function. Recent suggestions of nanoscale heat confinement on the surface of synthetic and biogenic magnetic nanoparticles during heating by radiofrequency alternating magnetic fields have generated intense interest due to the potential utility of this phenomenon in non-invasive control of biomolecular and cellular function. However, such confinement would represent a significant departure from classical heat transfer theory. We present an experimental investigation of nanoscale heat confinement on the surface of several types of iron oxide nanoparticles commonly used in biological research, using an all-optical method devoid of potential artifacts present in previous studies. By simultaneously measuring the fluorescence of distinct thermochromic dyes attached to the particle surface or dissolved in the surrounding fluid during radiofrequency magnetic stimulation, we found no measurable difference between the nanoparticle surface temperature and that of the surrounding fluid for three distinct nanoparticle types. Furthermore, the metalloprotein ferritin produced no temperature increase on the protein surface, nor in the surrounding fluid. Experiments mimicking the designs of previous studies revealed potential sources of artifacts. These findings inform the use of magnetic nanoparticle hyperthermia in engineered cellular and molecular systems and can help direct future resources towards tractable avenues of magnetic control of cellular function.
", "doi": "10.7907/9QEJ-6H55", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13612", "collection": "thesis", "collection_id": "13612", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01062020-004548466", "type": "thesis", "title": "Effects of Sensory Experience on Early Stages of Olfactory Processing in the Fruit Fly", "author": [ { "family_name": "Gugel", "given_name": "Zhannetta V.", "orcid": "0000-0003-1082-3281", "clpid": "Gugel-Zhannetta-V" } ], "thesis_advisor": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" } ], "thesis_committee": [ { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Plasticity is widely studied across different sensory systems and behavioral paradigms, but the underlying mechanisms are varied and incompletely understood. Previous work in the fruit fly Drosophila melanogaster reported changes in odor preference and walking behavior after chronic odor exposure during early adulthood. Here, we investigated the hypothesis that changes in behavior reflect changes in how odors are encoded in the first two layers of the fly olfactory circuit. We chronically exposed flies to naturalistic odor stimuli that selectively and robustly activate a single olfactory receptor neuron (ORN) class. We then performed targeted intracellular recordings from genetically identified second-order olfactory projection neurons (PNs) that either receive direct input from the activated ORN class, or receive indirect activity (via local lateral circuitry), during chronic odor exposure. In addition, we used existing reagents to create a novel optical method to characterize ORN-PN synaptic strength. We find that the fly antennal lobe is resistant to plasticity, with a few exceptions. Of the odors we tested, we find that rearing in trans-2-hexenal, a leaf aldehyde that selectively activates ab4a ORNs, weakly enhanced odor responses in some PNs. The effects of rearing on PNs were not explained by ORN odor responses or changes in ORN-PN synaptic strength. We find evidence that lateral excitation may increase across glomeruli following rearing, suggesting that some odors may alter PN responses globally. We discuss possible reasons for differences between our observations and prior work on olfactory plasticity in this circuit, which has been conducted primarily in the context of exposures to much higher, non-naturalistic concentrations of odor. Our results point to the stability of insect sensory circuits in the face of large perturbations in the sensory environment.
\r\n\r\n\u2028\u2028During our optical stimulation experiments, we find that driving Chrimson expression may abolish odor responses in some ORNs. We include sample data highlighting this observation in a population of pb1a olfactory neurons. Lastly, we include antennal local field potential recordings in response to a variety of odor concentrations to help guide future experiments seeking isointense odor panels.
", "doi": "10.7907/e39b-w024", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13695", "collection": "thesis", "collection_id": "13695", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05032020-101047008", "primary_object_url": { "basename": "Processing at Primary Chemosensory Neurons.pdf", "content": "final", "filesize": 3226385, "license": "other", "mime_type": "application/pdf", "url": "/13695/1/Processing at Primary Chemosensory Neurons.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Processing at Primary Chemosensory Neurons", "author": [ { "family_name": "Zocchi", "given_name": "Dhruv Sergio", "clpid": "Zocchi-Dhruv-Sergio" } ], "thesis_advisor": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Oka", "given_name": "Yuki", "orcid": "0000-0003-2686-0677", "clpid": "Oka-Yuki" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Oka", "given_name": "Yuki", "orcid": "0000-0003-2686-0677", "clpid": "Oka-Yuki" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Chemosensory perception involves the detection of chemical compounds. In animals, there are 2 chemical senses: taste, and olfaction. The two are related in that they utilize ligand-gated receptors, expressed in primary sensory neurons, to detect chemical stimuli from the surrounding environment. However, the processing of these inputs is quite different in the two systems, leading to divergent roles for olfaction and taste in sensory perception. This dissertation highlights some of these differences, by looking at processing of ethologically relevant stimuli at the very peripheral receptor neurons. The work is divided into 2 parts: water sensing by the mammalian taste system, and CO\u2082 sensing by the Drosophila olfactory system.
\r\n\r\nIn Chapter 1, I talk about water sensing in the mammalian taste system. Initiation of drinking behavior relies on peripheral water detection. It is likely that this detection is mediated, at least in part, by the taste system. Here, I have shown that acid-sensing taste receptor cells (TRCs) that were previously suggested as the sensors for sour taste, also respond to water. This response is mediated by a bicarbonate-dependent molecular mechanism, likely involving the Carbonic Anhydrase enzyme family. Furthermore, optogenetic stimulation of the acid-sensing TRCs in thirsty animals induces robust licking responses towards the light source, even in the absence of water. Conversely, thirsty animals lacking functional acid-sensing TRCs show compromised discrimination between water and non-aqueous fluids. Taken together, this work reveals the cellular mechanism of water detection by the mammalian taste system.
\r\n\r\nIn chapter 2, I talk about CO\u2082 sensing in the fruit fly. The Drosophila olfactory system responds to most odors with the activation of a large subset of its olfactory receptors (ORs). This broad activation is a consequence of the ORs having affinity to multiple chemical compounds. In contrast, a small number of odors, like CO\u2082, elicit responses in only single ORs. These ORs are, in contrast to most ORs, very narrowly tuned, generally responding only to that one odor. It has been assumed up until now that the specificity of these unique ORs is inherited by the olfactory receptor neurons (ORNs) they are expressed in, and even in the projection neurons (PNs), that the ORNs synapse onto. I show here that CO\u2082, though it activates only a single OR, the GR63a/GR21a hetero-dimer complex, actually activates multiple ORN axon terminals. This activation is due to lateral excitatory connections between axon terminals of the GR63a/GR21a expressing ORNs, and at least 4 other ORN types. Focusing on one of these ORNs, Ab1B, I show the lateral connections bypass the ORN cell bodies, only driving responses at the axon terminals. Consequently, Ab1B ORN axon terminals receive 2 sources of excitatory input, a feed-forward excitation from its endogenous OR, and a lateral excitation from GR63a/GR21a. This effectively divides the ORN into 2 compartments, distinct in their odor tuning. Finally, I show that lateral excitation is a general feature of the ORN circuit by silencing the feed-forward input of another ORN class, Ab1A. The Ab1A cell body is completely silent, but the axon terminals retain odor responses from lateral excitatory inputs. Thus, there is a lateral flow of odor information between multiple ORNs of the Drosophila olfactory system.
", "doi": "10.7907/yshd-3195", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13659", "collection": "thesis", "collection_id": "13659", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03122020-231054692", "primary_object_url": { "basename": "Yonil Jung__BMB_Dissertation_v8.pdf", "content": "final", "filesize": 7088308, "license": "other", "mime_type": "application/pdf", "url": "/13659/1/Yonil Jung__BMB_Dissertation_v8.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Neurons that Control Social States in Drosophila melanogaster", "author": [ { "family_name": "Jung", "given_name": "Yonil", "orcid": "0000-0002-1673-4450", "clpid": "Jung-Yonil" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" }, { "family_name": "Gradinaru", "given_name": "Viviana", "clpid": "Gradinaru-V" }, { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Animal behaviors are influences not only by the immediate stimuli they are receiving but also by internal states. Internal states such as fear, hunger, and arousal can change subjective \"feeling\", and result in complex behavioral outcome even if animals receive the same stimuli. In most cases, these state-dependent behavioral changes persist long after the sensory input that caused internal state change is removed, and affect future behavior, reflexing previous experience. This feature of state-control allows animals to adapt their behavior to be more suitable for their internal demands.
\r\n\r\nThe influence of the internal state on animal behavior has been emphasized for decades. There are multiple studies and attempts to identify persistent neuronal mechanisms which are the important feature of the internal state. However, how persistency makes the behavioral state interact with behavioral process to induce input/output relationship has been largely unknown. In addition, it is not clear what the behavioral functions of the persistence are, and what the circuit implementation of persistent activity is. Are there neurons that are persistently activated by external stimulus? Here we approached these questions by investigating social state of fruit flies, Drosophila melanogaster.
\r\n\r\nFruit flies exhibit complex social behaviors that are appropriate for given social cues. For example, male flies show courtship behavior toward female flies, and show aggressive behavior such as wing threat and fighting when they encounter opponent male files. Previous studies have been focused on what sensory cues induce these behaviors: detection of female specific pheromones, 7,11-HD, causes male files to court, and male specific pheromone, cVA, induces inter-male aggression. In this study, we have focused more on how these cues might affect internal state changes rather than immediate behavioral response.
\r\n\r\nStudying persistent social state change has been challenging due to the difficulty of precise, time-resolved presentation of the social cues. For instance, courtship behaviors require constant presence of female object toward which male flies show oriented behavior. The male-male aggressive behaviors such as lunging and tussling require constant interaction between two animals, and removal of opponent male fly is technically impossible. Therefore, we first developed an optogenetic tool in fly systems to study persistent feature of the social state change to mimic transient presentation of the social cue. In Chapter II, we describe an optogenetic tool that allows the manipulation of neural activity in a freely moving fly. We used Red activatable Channelrhodopsin (ReachR), which enabled us to manipulate activation of neurons in freely behaving adult flies in millisecond precision without interfering normal visual function. Using such an activation tool, we show that activation of female sensing neurons, P1 neurons, induces persistent courtship behaviors in male flies that last several minutes after the stimulation of P1 neurons.
\r\n\r\nAlthough we show that persistent internal state change can be induced by transient stimulation of the sensory cues in Chapter II, the circuit implementation of such a persistency is not clear. In Chapter III, we show that activation of P1 neurons triggers persistent activity in its downstream neurons, pCd neurons, that is necessary for the persistent social behavior induced by transient social behaviors. Interestingly, manipulation of the pCd neurons do not affect immediate behavioral response that are shown during the presentation of social cues (P1 stimulation), implying that there are parallel and dissociable pathways for the immediate response and enduring response derived from persistent internal state change, although these responses are caused by common cue. Although the neural mechanism to encode persistent activity is still unclear, this finding shows how internal state and command pathway interact with each other to affect behavioral outcome.
\r\n\r\nAltogether, these findings described in this dissertation offer new insights for future researchers to understand behavioral state control.
\r\n", "doi": "10.7907/pard-ed88", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13743", "collection": "thesis", "collection_id": "13743", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05302020-143859367", "primary_object_url": { "basename": "ThesisJanisHesse2020_ver6.pdf", "content": "final", "filesize": 7512821, "license": "other", "mime_type": "application/pdf", "url": "/13743/23/ThesisJanisHesse2020_ver6.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Neural Construction of Conscious Perception", "author": [ { "family_name": "Hesse", "given_name": "Janis Karan", "orcid": "0000-0003-0405-8632", "clpid": "Hesse-Janis-Karan" } ], "thesis_advisor": [ { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" }, { "family_name": "Rutishauser", "given_name": "Ueli", "orcid": "0000-0002-9207-7069", "clpid": "Rutishauser-U" }, { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Out of a myriad of sensory stimulations, our brain constructs a unified, self-consistent reality that we consciously experience. Little is known about how or where in the brain\u2019s processing stream of physical input a conscious percept emerges into awareness. A remarkable property of conscious perception is that even though external input is often ambiguous, the perceptual interpretation of the world that our brain generates is consistent across multiple layers of representation, e.g., figure-ground segmentation and object identity. We thus set out to study how the interaction between different nodes in the brain generates and propagates new conscious percepts. Since the code of object identity is already well-understood, in particular for faces as reviewed in this thesis, we decided to get a handle on segmentation signals first. It turned out that consistent segmentation signals are hard to find, however, we found functionally defined modules in the brain that contained consistent cells from which figure-ground signals can be decoded. We next investigated whether face cells in object recognition areas actually encode the conscious percept of a face or are just passive filters of visual input. To distill conscious perception from other cognitive processes, such as decision making, introspection, and reporting of the percept, which often accompany new conscious percepts, we developed a no-report binocular rivalry paradigm that relies on an active fixation task rather than report, and therefore eliminates these confounding factors. We found that face patches in inferotemporal cortex indeed encode the conscious percept of a face. Using novel high-yield electrodes, we were able to decode what the animal was consciously perceiving at a given time. Preliminary and future experiments of population recordings from multiple nodes of the cortical hierarchy simultaneously promise to go beyond correlates of consciousness and reveal the mechanisms of how and where conscious percepts are constructed.
", "doi": "10.7907/07r8-0845", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13765", "collection": "thesis", "collection_id": "13765", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06012020-165101402", "type": "thesis", "title": "Visual Computations in the Superior Colliculus", "author": [ { "family_name": "Lee", "given_name": "Kyu Hyun", "orcid": "0000-0001-6483-9444", "clpid": "Lee-Kyu-Hyun" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Tsao", "given_name": "Doris Y.", "clpid": "Tsao-D-Y" }, { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" }, { "family_name": "Rutishauser", "given_name": "Ueli", "clpid": "Rutishauser-U" }, { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis presents two projects related to large-scale extracellular recordings of neural signals. The first project asks how the brain sifts the onslaught of sensory information to identify the few bits that are relevant for guiding behavior. This question is studied in the context of the looming reaction, an innate defensive behavior against an approaching aerial predator. Interestingly, the mouse responds very selectively to the looming stimulus regardless of changes in orthogonal features, such as its position. The neural basis of this phenomenon is investigated with extracellular recordings in the superior colliculus, a midbrain visual area known to mediate the looming reaction. A detailed analysis of the difference between the superficial and deeper layers of the superior colliculus highlights a core function of visual processing: to discard information intelligently.
\r\n\r\nThe second project presents electrode pooling, a novel method to increase the yield of extracellular recordings with the modern silicon electrode array. The fundamental constraint of wire volume in these devices is identified, and a solution that makes use of the switching circuitry and the sparseness of the neural signal in the time axis is described. Specifically, the method proposes to intelligently choose many recording sites that carry signal and connect them to a single wire via manipulating the switches. This pooled recording is subsequently un-mixed by a spike-sorting algorithm. The method is implemented in a state-of-the-art silicon neural probe, and its effect on signal and noise is analyzed by theory and experiment. Recommendations on the design of silicon devices are made to facilitate the incorporation of this method in the future.
", "doi": "10.7907/zn2j-m319", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13808", "collection": "thesis", "collection_id": "13808", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06092020-120629159", "type": "thesis", "title": "From Restoring Human Vision to Enhancing Computer Vision", "author": [ { "family_name": "Liu", "given_name": "Yang", "orcid": "0000-0002-8155-9134", "clpid": "Liu-Yang-CNS" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" }, { "family_name": "Siapas", "given_name": "Athanassios G.", "clpid": "Siapas-A-G" }, { "family_name": "Yue", "given_name": "Yisong", "clpid": "Yue-Yisong" }, { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The central theme of this work is enabling vision, which includes two subtopics: restoring vision for blind humans, and enhancing computer vision models in visual recognition. Chapter 1 first provides a gentle introduction to relevant high level principles of human visual computations and summarizes two fundamental questions that vision answers: \"what\" and \"where.\" Chapters 2, 3, and 4 contain three published projects that are anchored by those two fundamental questions.
\r\n \r\nChapter 2 introduces a cognitive assistant to restore visual function for blind humans by focusing on an interface powered by audio augmented reality. The assistant communicates the \"what\" and \"where\" aspects of visual scenes by a combination of natural language and spatialized sound. We experimentally demonstrated that the assistant enables many aspects of visual functions for naive blind users.
\r\n \r\nChapters 3 and 4 develop data augmentation methods to address the data inefficiency problem in neural network based computer visual recognition models. In Chapter 3, a 3D-simulation based data augmentation method is developed for improving the generalization of visual classification models for rare classes. In Chapter 4, a fast and efficient data augmentation method is developed for the newly formulated panoptic segmentation task. The method improves performance of state-of-the-art panoptic segmentation models and generalizes across dataset domains, sizes, model architectures, and backbones.
", "doi": "10.7907/sq58-z682", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:13612", "collection": "thesis", "collection_id": "13612", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01062020-004548466", "type": "thesis", "title": "Effects of Sensory Experience on Early Stages of Olfactory Processing in the Fruit Fly", "author": [ { "family_name": "Gugel", "given_name": "Zhannetta V.", "orcid": "0000-0003-1082-3281", "clpid": "Gugel-Zhannetta-V" } ], "thesis_advisor": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" } ], "thesis_committee": [ { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Plasticity is widely studied across different sensory systems and behavioral paradigms, but the underlying mechanisms are varied and incompletely understood. Previous work in the fruit fly Drosophila melanogaster reported changes in odor preference and walking behavior after chronic odor exposure during early adulthood. Here, we investigated the hypothesis that changes in behavior reflect changes in how odors are encoded in the first two layers of the fly olfactory circuit. We chronically exposed flies to naturalistic odor stimuli that selectively and robustly activate a single olfactory receptor neuron (ORN) class. We then performed targeted intracellular recordings from genetically identified second-order olfactory projection neurons (PNs) that either receive direct input from the activated ORN class, or receive indirect activity (via local lateral circuitry), during chronic odor exposure. In addition, we used existing reagents to create a novel optical method to characterize ORN-PN synaptic strength. We find that the fly antennal lobe is resistant to plasticity, with a few exceptions. Of the odors we tested, we find that rearing in trans-2-hexenal, a leaf aldehyde that selectively activates ab4a ORNs, weakly enhanced odor responses in some PNs. The effects of rearing on PNs were not explained by ORN odor responses or changes in ORN-PN synaptic strength. We find evidence that lateral excitation may increase across glomeruli following rearing, suggesting that some odors may alter PN responses globally. We discuss possible reasons for differences between our observations and prior work on olfactory plasticity in this circuit, which has been conducted primarily in the context of exposures to much higher, non-naturalistic concentrations of odor. Our results point to the stability of insect sensory circuits in the face of large perturbations in the sensory environment.
\r\n\r\n\u2028\u2028During our optical stimulation experiments, we find that driving Chrimson expression may abolish odor responses in some ORNs. We include sample data highlighting this observation in a population of pb1a olfactory neurons. Lastly, we include antennal local field potential recordings in response to a variety of odor concentrations to help guide future experiments seeking isointense odor panels.
", "doi": "10.7907/e39b-w024", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:11005", "collection": "thesis", "collection_id": "11005", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06012018-150815346", "primary_object_url": { "basename": "YongJunLin2017Thesis_v41_YJL_20180601.pdf", "content": "final", "filesize": 3228317, "license": "other", "mime_type": "application/pdf", "url": "/11005/1/YongJunLin2017Thesis_v41_YJL_20180601.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Human Duration Perception Mechanisms in the Subsecond Range: Psychophysics and Electroencephalography Investigations", "author": [ { "family_name": "Lin", "given_name": "Yong-Jun", "orcid": "0000-0003-1239-5217", "clpid": "Lin-Yong-Jun" } ], "thesis_advisor": [ { "family_name": "Shimojo", "given_name": "Shinsuke", "clpid": "Shimojo-S" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" }, { "family_name": "O'Doherty", "given_name": "John P.", "clpid": "O'Doherty-J-P" }, { "family_name": "Yun", "given_name": "Kyongsik", "clpid": "Yun-Kyongsik" }, { "family_name": "Shimojo", "given_name": "Shinsuke", "clpid": "Shimojo-S" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "In a world full of fleeting events, how do humans perceive time intervals as short as half a second? Unlike primary senses, there are no time receptors. Is sub-second time perception reconstructed from memory traces in the primary senses, or based on the output of a modality-independent internal clock? In analogy to bugs in computer programs or mutations in genetics studies, I studied two types of subjective time warp illusions in order to understand how time perception normally works. One illusion that I examined is called oddball chronostasis, which is a duration distortion effect that happens to an unusual item. The other illusion is called debut chronostasis, which is a time warp effect that occurs to the first item among other identical ones.
\r\n\r\nRegarding oddball chronostasis, we solved a theoretical dispute over its underlying mechanisms and dissociated three causes. The necessary component is top-down attention to the target item. The other two components are contingent factors. This suggests that a pure sensory modality-dependent view of time perception mechanisms is less likely.\r\nRegarding debut chronostasis, we discovered auditory debut chronostasis and found that its illusion strength is about the same as the visual case. At first glance, this seems to suggest that time perception is independent of the primary sensory modalities. However, when visual and auditory events were compared against each other (inter-modal comparison), debut chronostasis disappeared. Therefore, modality-dependent mechanisms of time perception do exist. Further, we found a special factor that could counteract debut chronostasis and thus re-interpreted the main cause of debut chronostasis as internal duration template uncertainty. By examining both intra- and inter-modal comparisons, this uncertainty effect turned out to be a modality-independent effect. Therefore, modality-independent mechanisms of time perception also exist.
\r\n\r\nIn conclusion, this dissertation work contributed to novel theoretical understanding of two types of time perception illusions. Unlike many simplified theories in the literature either holding a modality-dependent or independent view, our findings altogether indicate that time perception involves both intra- and supra-modal stages. Future experimental work could thus target on separating intra- and supra-modal time perception mechanisms.
", "doi": "10.7907/KGG5-9375", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:9354", "collection": "thesis", "collection_id": "9354", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01042016-124746578", "type": "thesis", "title": "The Physiology and Computation of Pyramidal Neurons", "author": [ { "family_name": "Shai", "given_name": "Adam S.", "clpid": "Shai-Adam-S" } ], "thesis_advisor": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "thesis_committee": [ { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" }, { "family_name": "Koch", "given_name": "Christof", "orcid": "0000-0001-6482-8067", "clpid": "Koch-C" }, { "family_name": "Anastassiou", "given_name": "Costas", "clpid": "Anastassiou-C" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Tsao", "given_name": "Doris Y.", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "A variety of neural signals have been measured as correlates to consciousness. In particular, late current sinks in layer 1, distributed activity across the cortex, and feedback processing have all been implicated. What are the physiological underpinnings of these signals? What computational role do they play in the brain? Why do they correlate to consciousness? This thesis begins to answer these questions by focusing on the pyramidal neuron. As the primary communicator of long-range feedforward and feedback signals in the cortex, the pyramidal neuron is set up to play an important role in establishing distributed representations. Additionally, the dendritic extent, reaching layer 1, is well situated to receive feedback inputs and contribute to current sinks in the upper layers. An investigation of pyramidal neuron physiology is therefore necessary to understand how the brain creates, and potentially uses, the neural correlates of consciousness. An important part of this thesis will be in establishing the computational role that dendritic physiology plays. In order to do this, a combined experimental and modeling approach is used.
\r\n\r\nThis thesis beings with single-cell experiments in layer 5 and layer 2/3 pyramidal neurons. In both cases, dendritic nonlinearities are characterized and found to be integral regulators of neural output. Particular attention is paid to calcium spikes and NMDA spikes, which both exist in the apical dendrites, considerable distances from the spike initiation zone. These experiments are then used to create detailed multicompartmental models. These models are used to test hypothesis regarding spatial distribution of membrane channels, to quantify the effects of certain experimental manipulations, and to establish the computational properties of the single cell. We find that the pyramidal neuron physiology can carry out a coincidence detection mechanism. Further abstraction of these models reveals potential mechanisms for spike time control, frequency modulation, and tuning. Finally, a set of experiments are carried out to establish the effect of long-range feedback inputs onto the pyramidal neuron. A final discussion then explores a potential way in which the physiology of pyramidal neurons can establish distributed representations, and contribute to consciousness.
", "doi": "10.7907/Z92R3PMW", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9721", "collection": "thesis", "collection_id": "9721", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05162016-100757711", "primary_object_url": { "basename": "BillehYN2016.pdf", "content": "final", "filesize": 32112258, "license": "other", "mime_type": "application/pdf", "url": "/9721/1/BillehYN2016.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Functional, Clustered, Feedforward, and Mesoscale Brain Networks", "author": [ { "family_name": "Billeh", "given_name": "Yazan Nicola", "orcid": "0000-0001-5200-4992", "clpid": "Billeh-Yazan-Nicola" } ], "thesis_advisor": [ { "family_name": "Koch", "given_name": "Christof", "orcid": "0000-0001-6482-8067", "clpid": "Koch-C" } ], "thesis_committee": [ { "family_name": "Siapas", "given_name": "Athanassios G.", "orcid": "0000-0001-8837-678X", "clpid": "Siapas-A-G" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Koch", "given_name": "Christof", "orcid": "0000-0001-6482-8067", "clpid": "Koch-C" }, { "family_name": "Meister", "given_name": "Markus", "orcid": "0000-0003-2136-6506", "clpid": "Meister-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The brain is a network spanning multiple scales from subcellular to macroscopic. In this thesis I present four projects studying brain networks at different levels of abstraction. The first involves determining a functional connectivity network based on neural spike trains and using a graph theoretical method to cluster groups of neurons into putative cell assemblies. In the second project I model neural networks at a microscopic level. Using diferent clustered wiring schemes, I show that almost identical spatiotemporal activity patterns can be observed, demonstrating that there is a broad neuro-architectural basis to attain structured spatiotemporal dynamics. Remarkably, irrespective of the precise topological mechanism, this behavior can be predicted by examining the spectral properties of the synaptic weight matrix. The third project introduces, via two circuit architectures, a new paradigm for feedforward processing in which inhibitory neurons have the complex and pivotal role in governing information flow in cortical network models. Finally, I analyze axonal projections in sleep deprived mice using data collected as part of the Allen Institute's Mesoscopic Connectivity Atlas. After normalizing for experimental variability, the results indicate there is no single explanatory difference in the mesoscale network between control and sleep deprived mice. Using machine learning techniques, however, animal classification could be done at levels significantly above chance. This reveals that intricate changes in connectivity do occur due to chronic sleep deprivation.", "doi": "10.7907/Z9DB7ZSX", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9754", "collection": "thesis", "collection_id": "9754", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05252016-140422108", "primary_object_url": { "basename": "ChenBo2016.pdf", "content": "final", "filesize": 4706009, "license": "other", "mime_type": "application/pdf", "url": "/9754/38/ChenBo2016.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Quantum of Vision", "author": [ { "family_name": "Chen", "given_name": "Bo", "orcid": "0000-0001-5566-7361", "clpid": "Chen-Bo" } ], "thesis_advisor": [ { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "thesis_committee": [ { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" }, { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" }, { "family_name": "Kostina", "given_name": "Victoria", "clpid": "Kostina-V" }, { "family_name": "Rutishauser", "given_name": "Ueli", "clpid": "Rutishauser-U" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Visual inputs to artificial and biological visual systems are often quantized: cameras accumulate photons from the visual world, and the brain receives action potentials from visual sensory neurons. Collecting more information quanta leads to a longer acquisition time and better performance. In many visual tasks, collecting a small number of quanta is sufficient to solve the task well. The ability to determine the right number of quanta is pivotal in situations where visual information is costly to obtain, such as photon-starved or time-critical environments. In these situations, conventional vision systems that always collect a fixed and large amount of information are infeasible. I develop a framework that judiciously determines the number of information quanta to observe based on the cost of observation and the requirement for accuracy. The framework implements the optimal speed versus accuracy tradeoff when two assumptions are met, namely that the task is fully specified probabilistically and constant over time. I also extend the framework to address scenarios that violate the assumptions. I deploy the framework to three recognition tasks: visual search (where both assumptions are satisfied), scotopic visual recognition (where the model is not specified), and visual discrimination with unknown stimulus onset (where the model is dynamic over time). Scotopic classification experiments suggest that the framework leads to dramatic improvement in photon-efficiency compared to conventional computer vision algorithms. Human psychophysics experiments confirmed that the framework provides a parsimonious and versatile explanation for human behavior under time pressure in both static and dynamic environments.", "doi": "10.7907/Z9057CWS", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:8528", "collection": "thesis", "collection_id": "8528", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06292014-232713483", "primary_object_url": { "basename": "Rell_Parker_Complete_Thesis_2015.pdf", "content": "final", "filesize": 27520331, "license": "other", "mime_type": "application/pdf", "url": "/8528/1/Rell_Parker_Complete_Thesis_2015.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Lynx1 Modulation of Nicotinic Acetylcholine Receptors", "author": [ { "family_name": "Parker", "given_name": "Rell Lin", "clpid": "Parker-Rell-Lin" } ], "thesis_advisor": [ { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "David C.", "clpid": "Chan-D-C" }, { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" }, { "family_name": "Prober", "given_name": "David A.", "clpid": "Prober-D-A" }, { "family_name": "Lester", "given_name": "Henry A.", "clpid": "Lester-H-A" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Nicotinic receptors are the target of nicotine in the brain. They are pentameric ion channels. The pentamer structure allows many combinations of receptors to be formed. These various subtypes exhibit specific properties determined by their subunit composition. Each brain region contains a fixed complement of nicotinic receptor subunits. The midbrain region is of particular interest because the dopaminergic neurons of the midbrain express several subtypes of nicotinic receptors, and these dopaminergic neurons are important for the rewarding effects of nicotine. The \u03b16 nicotinic receptor subunit has garnered intense interest because it is present in dopaminergic neurons but very few other brain regions. With its specific and limited presence in the brain, targeting this subtype of nicotinic receptor may prove advantageous as a method for smoking cessation. However, we do not fully understand the trafficking and membrane localization of this receptor or its effects on dopamine release in the striatum. We hypothesized that lynx1, a known modulator of other nicotinic receptor subtypes, is important for the proper function of \u03b16 nicotinic receptors. lynx1 has been found to act upon several classes of nicotinic receptors, such as \u03b14\u03b22 and \u03b17, the two most common subtypes in the brain. To determine whether lynx1 affects \u03b16 containing nicotinic receptors we used biochemistry, patch clamp electrophysiology, fast scan cyclic voltammetry, and mouse behavior. We found that lynx1 has effects on \u03b16 containing nicotinic receptors, but the effects were subtle. This thesis will detail the observed effects of lynx1 on \u03b16 nicotinic receptors.", "doi": "10.7907/Z9HM56DT", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:7923", "collection": "thesis", "collection_id": "7923", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08162013-150835965", "primary_object_url": { "basename": "suver_marie_2013_thesis.pdf", "content": "final", "filesize": 17971044, "license": "other", "mime_type": "application/pdf", "url": "/7923/1/suver_marie_2013_thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Octopamine Neurons Mediate Flight-Induced Modulation of Visual Processing in Drosophila melanogaster", "author": [ { "family_name": "Suver", "given_name": "Marie Patricia", "clpid": "Suver-Marie-Patricia" } ], "thesis_advisor": [ { "family_name": "Dickinson", "given_name": "Michael H.", "clpid": "Dickinson-M-H" } ], "thesis_committee": [ { "family_name": "Siapas", "given_name": "Athanassios G.", "clpid": "Siapas-A-G" }, { "family_name": "Meister", "given_name": "Markus", "clpid": "Meister-M" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" }, { "family_name": "Dickinson", "given_name": "Michael H.", "clpid": "Dickinson-M-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Activity-dependent modulation of sensory systems has been documented in many organisms, and is likely to be essential for appropriate processing of information during different behavioral states. However, the mechanisms underlying these phenomena, and often their functional consequences, remain poorly characterized. I investigated the role of octopamine neurons in the flight-dependent modulation observed in visual interneurons in the fruit fly Drosophila melanogaster. The vertical system (VS) cells exhibit a boost in their response to visual motion during flight compared to quiescence. Pharmacological application of octopamine evokes responses in quiescent flies that mimic those observed during flight, and octopamine neurons that project to the optic lobes increase in activity during flight. Using genetic tools to manipulate the activity of octopamine neurons, I find that they are both necessary and sufficient for the flight-induced visual boost. This work provides the first evidence that endogenous release of octopamine is involved in state-dependent modulation of visual interneurons in flies. Further, I investigated the role of a single pair of octopamine neurons that project to the optic lobes, and found no evidence that chemical synaptic transmission via these neurons is necessary for the flight boost. However, I found some evidence that activation of these neurons may contribute to the flight boost. Wind stimuli alone are sufficient to generate transient increases in the VS cell response to motion vision, but result in no increase in baseline membrane potential. These results suggest that the flight boost originates not from a central command signal during flight, but from mechanosensory stimuli relayed via the octopamine system. Lastly, in an attempt to understand the functional consequences of the flight boost observed in visual interneurons, we measured the effect of inactivating octopamine neurons in freely flying flies. We found that flies whose octopamine neurons we silenced accelerate less than wild-type flies, consistent with the hypothesis that the flight boost we observe in VS cells is indicative of a gain control mechanism mediated by octopamine neurons. Together, this work serves as the basis for a mechanistic and functional understanding of octopaminergic modulation of vision in flying flies.", "doi": "10.7907/DJKK-TC21", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" } ]