Insects exhibit extraordinary behavioral diversity from rapid sensorimotor control required for flight to coordinated behavior across large societies. While some behaviors are best studied in controlled lab settings and require precise fine-grained measurements, others demand long-term observations in more natural settings that cannot be replicated in lab. In this thesis, I demonstrate the applications of computer vision to quantify insect behavior across scales, from the level of individuals to colonies, in both lab and field conditions.
\r\n\r\nIn the first part, I examine the role of mechanosensory cells, campaniform sensilla, on the stabilization response of the fruit fly, Drosophila melanogaster. Using tethered flies mounted on a rotating arena, I measure head and wing equilibrium responses using marker less pose estimation and edge tracking. By genetically silencing different subsets of campaniform sensilla, I show a linear relationship between the number of cells silenced and the magnitude of head and wing response, providing direct experimental evidence for their role in the equilibrium response.
\r\n \r\nIn the second part, I apply computer vision techniques to study colony scale movement dynamics at the nest entrance of the ant species, Liometopum occidentale, in the Angeles National Forest. I introduce a custom, low-cost, field deployable multisensory camera trap, called the Ethocam, and collect an extensive dataset of hourly videos from three ant nests spanning over 100 days. Using computer vision methods for detection and multi-object tracking, I quantify circadian activity patterns, \tdirectional traffic imbalances, environmental drivers of activity and walking speed, and spatiotemporal movement dynamics across distinct trails.
\r\n \r\nTogether, by integrating lab experiments, long term field data, and quantitative analysis using computer vision, this thesis presents a general framework for studying insect behavior across scales in both controlled and natural environments.
", "doi": "10.7907/yphx-fh43", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17346", "collection": "thesis", "collection_id": "17346", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06012025-211102729", "primary_object_url": { "basename": "Thomas_Naragon_Thesis_revised.pdf", "content": "final", "filesize": 20342612, "license": "other", "mime_type": "application/pdf", "url": "/17346/2/Thomas_Naragon_Thesis_revised.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Cuticular Hydrocarbons in Myrmecophiles are a Mechanism of Symbiotic Entrenchment", "author": [ { "family_name": "Naragon", "given_name": "Thomas Houser", "orcid": "0000-0002-5373-4257", "clpid": "Naragon-Thomas-Houser" } ], "thesis_advisor": [ { "family_name": "Parker", "given_name": "Joseph", "orcid": "0000-0001-9598-2454", "clpid": "Parker-J" } ], "thesis_committee": [ { "family_name": "Chong", "given_name": "Shasha", "orcid": "0000-0002-5372-311X", "clpid": "Chong-Shasha" }, { "family_name": "Demirer", "given_name": "G\u00f6zde S.", "orcid": "0000-0002-3007-1489", "clpid": "Demirer-G\u00f6zde-S" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "orcid": "0000-0002-3680-4399", "clpid": "Ismagilov-R-F" }, { "family_name": "Parker", "given_name": "Joseph", "orcid": "0000-0001-9598-2454", "clpid": "Parker-J" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The velvety tree ant, Liometopum occidentale, hosts three myrmecophilous rove beetles, Sceptobius lativentris, Platyusa sonomae, and Liometoxenus newtonarum. The three beetles independently evolved to mimic the nestmate recognition pheromones of L. occidentale with varying degrees of accuracy. The accuracy of the mimicry determines the degree of integration of the beetles into nests of their host; P. sonomae achieves the least accurate mimicry and is located at the nest periphery, whereas S. lativentris employs the most accurate mimicry and has access to the entirety of the ant nest and its resources. The accuracy of the mimicry was found to be dependent on the mechanism by which it is achieved. P. sonomae synthesizes the pheromone blend de novo and S. lativentris acquires the pheromones from the host ant. The approach taken by S. lativentris is significant, because the class of chemicals used as nestmate recognition pheromones in ants play a more primary role, forming a desiccation barrier that coats the surface of all insects. In the transition into the nests of its hosts, which occurs after the pupal developmental stage, S. lativentris permanently shuts off its production of these anti-desiccation compounds, opting instead to steal them from its host. This high-fidelity mimicry comes at a cost. S. lativentris is locked into an obligate and irreversible dependence on L. occidentale, dying within a day away from its host ant.", "doi": "10.7907/s8ng-e309", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16245", "collection": "thesis", "collection_id": "16245", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11162023-182820794", "primary_object_url": { "basename": "SharanPRAKASH_BBE_thesis_final_text.pdf", "content": "final", "filesize": 785256, "license": "cc_by", "mime_type": "application/pdf", "url": "/16245/1/SharanPRAKASH_BBE_thesis_final_text.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Experimental and Neuroinformatic Definition of Neural Circuits in Caenorhabditis elegans", "author": [ { "family_name": "Prakash", "given_name": "Sharan Jagdish", "orcid": "0000-0003-1777-0987", "clpid": "Prakash-Sharan-Jagdish" } ], "thesis_advisor": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" } ], "thesis_committee": [ { "family_name": "Hay", "given_name": "Bruce A.", "orcid": "0000-0002-5486-0482", "clpid": "Hay-B-A" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Rothenberg", "given_name": "Ellen V.", "orcid": "0000-0002-3901-347X", "clpid": "Rothenberg-E-V" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The free-living nematode Caenorhabditidis elegans is an established model organism for research in molecular genetics, cell and developmental biology, evolution, and neuroscience. This thesis describes two research projects in C. elegans neuroscience. The first project concerns the challenge of synthesizing the accumulating neurobiological literature in C. elegans. I describe how an established framework for semantic modelling of cellular pathways can be adapted for semantic modelling of neural circuits and functional annotation of the nervous system, and its potential applications for systems neuroscience. A second portion describes a series of experiments investigating a decision-making process in C. elegans larval development that is under neuronal control. C. elegans larvae have the ability to decide among alternative developmental trajectories based on environmental conditions, that are detected via its nervous system. In this work, I describe the contribution of several neurons to this decision-making process, and our discoveries about the response properties of two neurons to ethologically relevant chemical stimuli.", "doi": "10.7907/bgvy-9p06", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16303", "collection": "thesis", "collection_id": "16303", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02262024-021912071", "primary_object_url": { "basename": "he_manni_2024_thesis_submit.pdf", "content": "final", "filesize": 31075794, "license": "other", "mime_type": "application/pdf", "url": "/16303/2/he_manni_2024_thesis_submit.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Entanglement-Enhanced Bioimaging and Sensing", "author": [ { "family_name": "He", "given_name": "Manni", "orcid": "0009-0001-4237-900X", "clpid": "He-Manni" } ], "thesis_advisor": [ { "family_name": "Cushing", "given_name": "Scott K.", "orcid": "0000-0003-3538-2259", "clpid": "Cushing-Scott-K" } ], "thesis_committee": [ { "family_name": "Wei", "given_name": "Lu", "orcid": "0000-0001-9170-2283", "clpid": "Wei-Lu" }, { "family_name": "Blake", "given_name": "Geoffrey A.", "orcid": "0000-0003-0787-1610", "clpid": "Blake-G-A" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Cushing", "given_name": "Scott K.", "orcid": "0000-0003-3538-2259", "clpid": "Cushing-Scott-K" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Studies of entangled light-matter interactions have been gaining momentum because of their potential applications in bioimaging and sensing. Entangled photons are predicted to linearize nonlinear optical processes and offer orders of magnitude of enhancement to the interaction cross sections. To investigate the validity of entanglement-enhanced bioimaging techniques, a continuous wave (CW)-powered, on-chip, broadband entangled light source based on periodically poled lithium tantalate (ppLT) was designed and characterized. This light source achieved femtosecond entangled correlation times comparable to classical ultrafast lasers with an unprecedented power of ~100 nW in near-infrared (NIR), which is a crucial first step toward fully integrated, thin-film lithium niobate (TFLN)-based, visible to NIR entangled photon sources. This light source was then used for subsequent spectroscopy/microscopy experiments to systematically investigate the feasibility of entanglement-enabled microscopy techniques such as entangled two-photon absorption (ETPA) microscopy and entangled fluorescence lifetime measurements. A novel method was developed to measure fluorescence from ETPA using a spectrotemporally resolved Michelson interferometer which is good at eliminating false signals due to one-photon absorption and scattering. Careful experimental attempts at detecting virtual-state mediated ETPA from rhodamine 6G (R6G) and resonance-enhanced ETPA from indocyanine green (ICG) were made, and the ETPA signals were found to be below the instrument detection limits and often masked by one-photon effects such as scattering and linear absorption. Instead, experimental upper bounds were placed on the ETPA cross sections of the studied molecules, with an emphasis on continued improvement of the light source and instrument detection limits. On-chip entangled fluorescence lifetime imaging microscopy (entangled-FLIM) has also been identified as a new future development focus. The feasibility of the technique was demonstrated via a proof-of-principle experiment which measured the fluorescence lifetime of ICG in various solvents. Using entangled photons produced from a CW laser, the lifetime measurement scheme achieved a temporal resolution of 50 ps and a minimum measurable lifetime of 365 ps, which can be used to distinguish most biologically relevant fluorophores in the corresponding wavelength range. This experiment is a critical first step toward scalable, high-throughput, wavelength-multiplexed, and on-chip FLIM or lifetime measurements which could be used in label-free health monitoring technologies.", "doi": "10.7907/3zg0-4135", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16516", "collection": "thesis", "collection_id": "16516", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06112024-013230923", "type": "thesis", "title": "The Role of Integral Gain and its Neuromuscular Implementation in the Flight Control System of Drosophila", "author": [ { "family_name": "Ponce", "given_name": "Francesca V.", "orcid": "0000-0002-9070-2780", "clpid": "Ponce-Francesca-V" } ], "thesis_advisor": [ { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "thesis_committee": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Siapas", "given_name": "Athanassios G.", "orcid": "0000-0001-8837-678X", "clpid": "Siapas-A-G" }, { "family_name": "Parker", "given_name": "Joseph", "orcid": "0000-0001-9598-2454", "clpid": "Parker-J" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Small flying insects, such as the fruit fly Drosophila melanogaster, can navigate along a relatively straight path for long distances. During these journeys, they need a long-range navigational strategy to maintain a constant heading over time, as well as stabilizing behaviors to deal with perturbations, such as a sudden gust of wind or a broken wing. In this work, I characterize a behavioral strategy flies use to maintain stable flight using a combination of experimental and control theoretic approaches. I then investigate how this control strategy is implemented in the flight motor system. In Chapter 1, I describe release-and-recapture experiments performed in the Mojave Desert to investigate how flies interact with the wind to travel long distances. These experiments provide key insight into the dispersal behavior of small insects and suggest that these animals employ a single algorithm that is functionally robust in both still air and under windy conditions. In Chapter 2, I present an extensive set of behavioral experiments showing that the optomotor response, a well-described stabilizing flight reflex, can be accurately modelled by a proportional-integral controller. I also show simulations that exemplify the potential functional advantage of this controller model in natural flight conditions. In Chapter 3, I show the results from muscle imaging experiments designed to investigate how the integral gain of a proportional integral controller might be implemented within the flight motor system. Finally, in Chapter 4, I summarize the main findings, and discuss the limitations of this work and future directions.
", "doi": "10.7907/j2mb-ka39", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16404", "collection": "thesis", "collection_id": "16404", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05212024-230922611", "primary_object_url": { "basename": "240522_zhang_mark_2024_thesis_final.pdf", "content": "final", "filesize": 8623620, "license": "other", "mime_type": "application/pdf", "url": "/16404/2/240522_zhang_mark_2024_thesis_final.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Bridging Sensory Perception to Developmental Decision Making in Caenorhabditis elegans", "author": [ { "family_name": "Zhang", "given_name": "Mark Guangde", "orcid": "0000-0002-0802-300X", "clpid": "Zhang-Mark-Guangde" } ], "thesis_advisor": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" } ], "thesis_committee": [ { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" }, { "family_name": "Rothenberg", "given_name": "Ellen V.", "orcid": "0000-0002-3901-347X", "clpid": "Rothenberg-E-V" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Amidst uncertain environmental flux, organisms must be able to appropriately adapt their physiology in response to or in preparation for harsh conditions. To accomplish this task, organisms need to accurately perceive current environmental cues, make informed decisions about how the future environmental landscape might unfold, and execute the genetic programs to manifest the proper physiological changes. As a prime example, the roundworm Caenorhabditis elegans makes multiple developmental decisions during its life cycle in response to environmental cues. During larval growth, C. elegans can forego reproductive growth and instead enter diapause (also called dauer), a developmentally arrested state resistant to environmental stress, in response to unfavorable growth conditions. The decisions to enter and exit dauer involve complex neurogenetic computations that integrate environmental cues, yet despite decades of research in the field of C. elegans dauer biology, we still do not fully understand how such sensory integration occurs. Furthermore, how the dauer entry and exit decisions compare and contrast to one another remains unclear.
\r\n \r\nIn this thesis, I comprehensively analyze the C. elegans dauer exit decision using behavioral analyses, neuronal imaging, and gene reporter technologies. In Chapter Two, I I demonstrate how, during dauer exit, the ASJ chemosensory neurons integrate food availability and population density at both the levels of neuronal calcium dynamics and gene expression. I show that expression of the insulin-like peptide encoding gene ins 6 within the ASJ neurons is responsive to dauer-relevant cues, dependent on ASJ neuronal activity, and participates in an autoregulatory feedback mechanism that enforces decision commitment. In Chapter Three, I analyze how steroid hormones are essential for the dauer exit decision, and I illustrate how the spatiotemporal dynamics of steroid hormone regulation during dauer exit compares with that of dauer entry. Taken together, this thesis significantly advances our knowledge of the C. elegans dauer exit decision and helps us better understand how animals coordinate decisions over long timescales in response to changing environments.
", "doi": "10.7907/hf7p-aa22", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16399", "collection": "thesis", "collection_id": "16399", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05202024-215640209", "primary_object_url": { "basename": "20240524_caltech_thesis_julian_wagner.pdf", "content": "final", "filesize": 8359789, "license": "other", "mime_type": "application/pdf", "url": "/16399/1/20240524_caltech_thesis_julian_wagner.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Uncovering Mechanisms of Host Recognition, Host Finding and Host Specificity", "author": [ { "family_name": "Wagner", "given_name": "Julian Morgan", "orcid": "0000-0003-3406-0450", "clpid": "Wagner-Julian-Morgan" } ], "thesis_advisor": [ { "family_name": "Parker", "given_name": "Joseph", "orcid": "0000-0001-9598-2454", "clpid": "Parker-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.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Pachter", "given_name": "Lior S.", "orcid": "0000-0002-9164-6231", "clpid": "Pachter-L" }, { "family_name": "Parker", "given_name": "Joseph", "orcid": "0000-0001-9598-2454", "clpid": "Parker-J" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Insect diversification is thought to have been catalyzed by widespread specialization on novel hosts\u2014a process underlying exceptional radiations of phytophagous beetles, lepidopterans, parasitoid wasps, and inordinate lineages of symbionts, predators, and other trophic specialists. The fidelity of such interspecies partnerships is often posited to arise from sensory tuning to host-derived cues, a model supported by studies of neural function in host-specific model species. Abundant literature on parasites also suggest that extrinsic factors, namely dispersal mechanisms and aggressiveness/acceptance from novel hosts, externally enforces host specificity. Here, I first review what is known about host specificity, why it arises and how it is controlled, and then explore how these factors influence the biology of myrmecophiles, the intimate symbiotic associates of ants. I then test the mechanisms of host specificity by investigating the chemosensory basis of symbiotic interactions between a myrmecophile rove beetle and its single, natural host ant species. I show that host cues trigger analogous behaviors in both the ant and myrmecophile. Cuticular hydrocarbons\u2014the ant's nestmate recognition pheromones\u2014elicit partner recognition in the myrmecophile and execution of ant grooming behavior that achieves chemical mimicry. The myrmecophile also follows host trail pheromones, permitting inter-colony dispersal. Remarkably, however, the myrmecophile performs these same adaptive behaviors with non-host ants separated by up to ~100-million years and shows minimal preference for its natural host over non-host ant species. Experimentally validated agent-based modelling supports a scenario in which specificity is enforced by physiological constraints on dispersal, and negative fitness interactions with alternative hosts, rather than via sensory tuning. Infrequent realization of latent compatibilities of specialists with alternative hosts may facilitate host switching, and the persistence and diversification of seemingly specialized clades over deep time.", "doi": "10.7907/k4b2-2n58", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16194", "collection": "thesis", "collection_id": "16194", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09282023-003458037", "primary_object_url": { "basename": "Andrew-Hill-thesis-230927.pdf", "content": "final", "filesize": 14206486, "license": "other", "mime_type": "application/pdf", "url": "/16194/1/Andrew-Hill-thesis-230927.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "The Genetic and Neuronal Substrates of Melatonin Signaling in Zebrafish Sleep", "author": [ { "family_name": "Hill", "given_name": "Andrew James", "orcid": "0000-0002-4621-0500", "clpid": "Hill-Andrew-James" } ], "thesis_advisor": [ { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" } ], "thesis_committee": [ { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Sleep is hypothesized to be regulated by two processes: a circadian drive, which communicates time of day to ensure that sleep is timed to the appropriate day/night phase, and a homeostatic drive, by which the propensity for sleep becomes stronger over the course of prolonged wakefulness. While studies suggest that adenosine and serotonin signaling in part mediate the homeostatic sleep drive, factors that act downstream of the circadian clock to promote sleep were unidentified until recently. Previous work in the Prober lab has shown that the nocturnal hormone melatonin acts downstream of the circadian rhythm to promote sleep in zebrafish. The downstream processes by which melatonin promotes sleep is poorly understood across all animal models. This is likely because melatonin research has been primarily conducted using nocturnal laboratory rodent models, in whom melatonin does not seem to play a role in sleep, and because of the widely held view that melatonin informs the circadian clock and does not promote sleep directly. In Chapter 1 of this thesis, I review some of the research conducted over the last 50 years that has informed our current understanding of melatonin and its role in sleep. In Chapter 2, I describe our efforts to use the zebrafish, in which melatonin is both potently sedating and essential for nightly sleep, to uncover some of the mechanisms by which melatonin might promote sleep. We found that melatonin acts through a particular melatonin receptor family called MT1, whereas melatonin receptors belonging to other families were dispensable for sleep. We show that MT1 receptors are expressed broadly throughout the zebrafish brain and are enriched in brain regions involved in sensory processing, particularly in those related to vision. We tested the hypothesis that melatonin promotes sleep, at least in part, by dampening visual responsiveness at night. We show that, separable from sleep, exogenous melatonin suppresses behavioral responses to light stimuli, and loss of endogenous melatonin results in day-like behavioral responses to light stimuli during the night. We are using whole brain imaging in live zebrafish to corroborate our behavioral results with neuronal GCaMP recordings. We hope that the findings presented here contribute to a greater understanding of melatonin\u2019s role in sleep, which may help enhance its value as a natural therapeutic aid.", "doi": "10.7907/4sba-6h56", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:15228", "collection": "thesis", "collection_id": "15228", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05292023-213541270", "type": "thesis", "title": "Genetically Encoded Biosensors for Ketamine and Other Rapidly Acting Antidepressants in Zebrafish and Cell Culture", "author": [ { "family_name": "Blumenfeld", "given_name": "Zachary", "orcid": "0000-0002-4627-5582", "clpid": "Blumenfeld-Zachary" } ], "thesis_advisor": [ { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" } ], "thesis_committee": [ { "family_name": "Adolphs", "given_name": "Ralph", "orcid": "0000-0002-8053-9692", "clpid": "Adolphs-R" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Over the past century, the development and use of treatments for depression has been one of the most important projects in both neuroscience and medicine. Not only is relatively little known about the underlying pathophysiology of major depressive disorder (MDD), a mechanistic understanding of the ways in which common antidepressants \u2014 such as selective serotonin reuptake inhibitors (SSRIs) \u2014 contribute to symptomatic relief remains elusive. Furthermore, the delay until typical antidepressant treatments take effect (a 'therapeutic lag' of weeks to months) presents a series of challenges to researchers in chemistry, neuroscience, pharmacology, and medicine, as the connection between apparent physiological changes and clinical benefit has yet to be established. The recent advent of a new class of drugs \u2014 rapidly acting antidepressants (RAADs), including the multi-purpose compound ketamine \u2014 which ameliorate symptoms within hours to days provides a crucial (if perplexing) perspective on the treatment of MDD and neuropsychiatric disorders more broadly. To answer questions concerning how various kinds of antidepressants might exert their effects, where those interactions take place, and what sorts of physiological changes drive clinical response, we have designed genetically encoded drug-specific intensity-based sensing fluorescent reporters (iDrugSnFRs) which are engineered to detect drugs of interest in both in vitro and in vivo applications. We have successfully evolved iDrugSnFRs for an array of RAADs (iRAADSnFRs) which detect pharmacologically relevant concentrations of their target drugs sensitively and specifically in both cell culture as well as in the nervous tissue of larval zebrafish. Another set of iDrugSnFRs for SSRIs has provided novel insights into the potential reasons for the aforementioned 'therapeutic lag' as well as side effects, while yet another set has provided a pharmacokinetic basis for the evaluation of smoking cessation drugs. In all, our findings lead us to posit that iDrugSnFRs can aid in the elucidation of mechanisms by which a wide variety of orally active pharmaceutical compounds operate as well as provide a crucial basis for the development of better medicines.
", "doi": "10.7907/4wtg-qb69", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:14414", "collection": "thesis", "collection_id": "14414", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10312021-193119771", "type": "thesis", "title": "Sparse Neural and Motor Networks Underlying Control in the Drosophila Flight System", "author": [ { "family_name": "de Souza", "given_name": "Alysha Maria", "clpid": "de-Souza-Alysha-Maria" } ], "thesis_advisor": [ { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "thesis_committee": [ { "family_name": "Siapas", "given_name": "Athanassios G.", "orcid": "0000-0001-8837-678X", "clpid": "Siapas-A-G" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Parker", "given_name": "Joseph", "orcid": "0000-0001-9598-2454", "clpid": "Parker-J" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "We often look to the natural world for inspiration in design and engineering. The fruit fly, Drosophila melanogaster, with approximately 100,000 neurons in its central nervous system (CNS) versus the roughly 100 billion neurons of the human brain, is relatively uncompromising in the richness of behaviors it is capable of performing given its comparatively sparse nervous system. It exhibits exceptional aerial agility, despite the steep aerodynamic constraints of miniaturization thanks to unique physiological and biomechanical thoracic adaptations. However, the mechanisms governing its sparse and precise flight control have remained largely inaccessible due to technological and geometric limitations, leaving many long-standing questions in the field of insect flight control unexplored. Recent advances in the field of molecular biology have created a vast toolkit for both optical imaging and genetic manipulation of cellular function. This revolution of genetic advances allows us to visualize changes in muscle activity in situ as fluorescent signals, to record from fluorescently targeted cells via electrophysiology or 2-photon imaging, and to optogenetically activate or silence the activity of targeted cells. This thesis utilizes recent technological and molecular advances to probe three key aspects of fly flight control: 1) the dynamic interactions of flight steering muscles to produce flight maneuvers, 2) the source of timing information for the structuring of the the motor phase code, an extremely temporally precise wingbeat-synchronous aspect neural firing, and 3) the mechanisms by which slow, graded descending visual process recruit the flight muscles.
\r\n\r\nIn the contents of the ensuing chapters I propose mechanisms for flight control pertaining to the wing muscles as well as their inputs. First, I describe the activities of each of the flight steering muscles in response to visual motion to generate movement in yaw, pitch, and roll (Chapter II). I then characterize the flexible individual dynamics and combinatorial timing of the system, and propose specific mechanisms by which interneurons rather than muscle physiology govern these adaptable firing patterns according to sensory inputs(Chapter II). Sensory inputs within this thesis take two forms: thoracic mechanosensory and timing information as well as descending visual input. I characterize mechanosensory and timing adaptations of an evolutionarily evolved hind wing, as well as the impact of haltere feedback to flight control (Chapter III). Lastly, I propose a mechanism by which descending visual commands produce graded outputs of the muscles.
", "doi": "10.7907/part-mf19", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14641", "collection": "thesis", "collection_id": "14641", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272022-195420095", "primary_object_url": { "basename": "Kajikawa_Koichiro_2022.pdf", "content": "final", "filesize": 63518649, "license": "other", "mime_type": "application/pdf", "url": "/14641/1/Kajikawa_Koichiro_2022.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Inhibition is the Hallmark of CA3 Intracellular Dynamics Around Awake Ripples", "author": [ { "family_name": "Kajikawa", "given_name": "Koichiro", "orcid": "0000-0002-8626-4407", "clpid": "Kajikawa-Koichiro" } ], "thesis_advisor": [ { "family_name": "Siapas", "given_name": "Athanassios G.", "orcid": "0000-0001-8837-678X", "clpid": "Siapas-A-G" } ], "thesis_committee": [ { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" }, { "family_name": "Andersen", "given_name": "Richard A.", "orcid": "0000-0002-7947-0472", "clpid": "Andersen-R-A" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Siapas", "given_name": "Athanassios G.", "orcid": "0000-0001-8837-678X", "clpid": "Siapas-A-G" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Hippocampal ripples are transient population bursts that structure cortico-hippocampal communication and play a central role in memory processing. However, the mechanisms controlling ripple initiation in behaving animals remain poorly understood. Here we combine multisite extracellular and whole cell recordings in awake mice to contrast the brain state and ripple modulation of subthreshold dynamics across hippocampal subfields. We find that entorhinal input to DG exhibits UP and DOWN dynamics with ripples occurring exclusively in UP states. While elevated cortical input in UP states generates depolarization in DG and CA1, it produces persistent hyperpolarization in CA3 neurons. Furthermore, growing inhibition is evident in CA3 throughout the course of the ripple buildup, while DG and CA1 neurons exhibit depolarization transients 100 ms before and during ripples. These observations highlight the importance of CA3 inhibition for ripple generation, while pre-ripple responses indicate a long and orchestrated ripple initiation process in the awake state.
", "doi": "10.7907/pwh5-7229", "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:14103", "collection": "thesis", "collection_id": "14103", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03112021-005902753", "type": "thesis", "title": "C. elegans Models of ASD-Associated Missense Variants", "author": [ { "family_name": "Wong", "given_name": "Wan-Rong", "orcid": "0000-0002-9757-8145", "clpid": "Wong-Wan-Rong" } ], "thesis_advisor": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" } ], "thesis_committee": [ { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" }, { "family_name": "Zinn", "given_name": "Kai George", "orcid": "0000-0002-6706-5605", "clpid": "Zinn-K-G" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The evolving next-generation sequencing technology accelerates the identification of disease-associated genetic variants. However, interpretation of these variants remains challenging, especially variants with subtle effects such as missense variants. Missense variants account for a large proportion of genetic variants in human diseases, including autism spectrum disorder (ASD). The causal relationship of most missense variants in the pathogenesis of ASD has not yet been demonstrated, and an experimental method systematically prioritizing missense alleles can gain crucial insight into the molecular basis for disease pathology. Therefore, I developed an in vivo multi-cellular system using Caenorhabditis elegans to systematically evaluate the functional consequences of disease-associated missense variants. I identified highly conserved human ASD-associated missense variants in their C. elegans orthologs, used a CRISPR/Cas9-mediated homology-directed knock-in strategy to generate missense mutants, and analyzed their impact on behaviors and development via several broad-spectrum assays. Overall, I generated 60 ASD-associated missense variants and characterized these missense mutant strains using a fecundity assay, an automated locomotor tracking system, and a chemotaxis assay. I found that 19% of the human disease-associated alleles have conserved loci in their C. elegans orthologs. Among the genes I tested, 64-70% of the missense variants predicted to perturb protein function showed detectable phenotypic changes in morphology, locomotion, or fecundity. Our results also revealed that missense mutants in different gene networks displayed distinct phenotypic profiles. Moreover, I focused on studying the genetic properties of missense variants on two ASD risk genes. I discovered the developmental defects in the ALDH1A3 C174Y missense mutation involved in the retinoic acid signaling pathway. I also identified a conserved missense residue lin-45(K565N), orthologous to human BRAF(K499N), which displayed a hypersensitive non-dominant phenotype in the diacetyl chemotaxis assay that was capable of being inhibited by RNAi. The finding suggests a potential gain-of-function allele in BRAF, especially in the sensory function. To sum up, I established a working pipeline to systematically identify and generate evolutionarily conserved ASD-associated missense mutants in C. elegans. This approach will help assess the impact of a single missense mutation in the whole organism and prioritize consequential missense variants for further intensive analysis in vertebrate models and human cells.
", "doi": "10.7907/y9gj-y034", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14056", "collection": "thesis", "collection_id": "14056", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01202021-155015733", "primary_object_url": { "basename": "Altermatt_Michael_2020_Thesis_Final.pdf", "content": "final", "filesize": 9956451, "license": "other", "mime_type": "application/pdf", "url": "/14056/1/Altermatt_Michael_2020_Thesis_Final.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Serotonergic Circuits: Role in Sleep and Enhanced Genetic Tools for Access and Optical Recording", "author": [ { "family_name": "Altermatt", "given_name": "Michael", "orcid": "0000-0003-2841-5374", "clpid": "Altermatt-Michael" } ], "thesis_advisor": [ { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" } ], "thesis_committee": [ { "family_name": "Prober", "given_name": "David A.", "orcid": "0000-0002-7371-4675", "clpid": "Prober-D-A" }, { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" }, { "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" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Overall, this thesis encompasses three main directions: the study of neural circuits in sleep (Chapter 2), the development and testing of tools for measuring neuromodulator release (Chapter 3), and methods for in vivo characterization of gene delivery vehicles (Chapter 5).
\r\n\r\nThe role of the neuromodulator serotonin in sleep has been debated for over 60 years. Until recently, the serotonergic system was widely thought to be part of the arousal system and promote wakefulness. In Chapter 2, we investigate the function of serotonin-producing neurons in murine and zebrafish sleep with tools featuring superior specificity and precision compared to previously employed techniques. Our results demonstrate that the serotonergic raphe are sleep-promoting and required for sleep homeostasis. Intriguingly, serotonergic neurons in mice can have opposing effects on sleep depending on the firing mode.
\r\n\r\nThe release of serotonin from neurons can be regulated by the frequency of neuronal firing and can occur at classical synapses, varicosities, soma, and dendrites. Further examination of the complex signaling mechanism of serotonin would benefit from tools capable of measuring the release of serotonin in vivo with long-term stability and high spatiotemporal resolution. To this end, we developed and characterized iSeroSnFR, an intensity-based genetically encoded serotonin indicator. In Chapter 3, we demonstrate that iSeroSnFR can detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep-wake transitions.
\r\n\r\nAdeno-associated viruses (AAVs) have been extensively used as gene delivery vehicles in basic neuroscience and gene therapy. However, optimization of transduction efficiency and target specificity remain a key challenge to overcome. Several AAV vector engineering approaches have been devised for this purpose and yield large collections of candidates that require further in vivo characterization. However, conventional characterization methods fall short with regard to in-depth cell type tropism analysis and/or high-throughput capabilities. In Chapter 5, we address this shortcoming with single-cell RNA sequencing technologies based on the Drop-seq method. We established an experimental and computational pipeline that allows us to profile the viral tropism of multiple AAV variants in parallel across numerous complex cell types.
", "doi": "10.7907/gfe2-w578", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "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" } ]