[ { "id": "authors:zb8x8-zck64", "collection": "authors", "collection_id": "zb8x8-zck64", "cite_using_url": "https://authors.library.caltech.edu/records/zb8x8-zck64", "type": "article", "title": "Large-scale high-density brain-wide neural recording in nonhuman primates", "author": [ { "family_name": "Trautmann", "given_name": "Eric M.", "orcid": "0000-0001-5552-2023", "clpid": "Trautmann-Eric-M" }, { "family_name": "Hesse", "given_name": "Janis K.", "orcid": "0000-0003-0405-8632", "clpid": "Hesse-Janis-K" }, { "family_name": "Stine", "given_name": "Gabriel M.", "orcid": "0000-0003-4906-0461", "clpid": "Stine-Gabriel-M" }, { "family_name": "Xia", "given_name": "Ruobing", "orcid": "0000-0002-1460-5882", "clpid": "Xia-Ruobing" }, { "family_name": "Zhu", "given_name": "Shude", "orcid": "0000-0002-8674-9607", "clpid": "Zhu-Shude" }, { "family_name": "O'Shea", "given_name": "Daniel J.", "orcid": "0000-0002-1366-1743", "clpid": "O'Shea-Daniel-J" }, { "family_name": "Karsh", "given_name": "Bill", "clpid": "Karsh-Bill" }, { "family_name": "Colonell", "given_name": "Jennifer", "clpid": "Colonell-Jennifer" }, { "family_name": "Lanfranchi", "given_name": "Frank F.", "orcid": "0000-0001-8176-320X", "clpid": "Lanfranchi-Frank-F" }, { "family_name": "Vyas", "given_name": "Saurabh", "orcid": "0000-0002-5406-3272", "clpid": "Vyas-Saurabh" }, { "family_name": "Zimnik", "given_name": "Andrew", "orcid": "0000-0002-8313-2476", "clpid": "Zimnik-Andrew" }, { "family_name": "Amematsro", "given_name": "Elom", "orcid": "0000-0003-4843-4513" }, { "family_name": "Steinmann", "given_name": "Natalie A.", "orcid": "0000-0002-6350-2038", "clpid": "Steinmann-Natalie-A" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Pachitariu", "given_name": "Marius", "orcid": "0000-0001-7106-814X" }, { "family_name": "Andrei", "given_name": "Alexandru", "clpid": "Andrei-Alexandru" }, { "family_name": "Mora Lopez", "given_name": "Carolina", "orcid": "0000-0003-4200-0001", "clpid": "Mora-Lopez-Carolina" }, { "family_name": "O'Callaghan", "given_name": "John", "orcid": "0000-0003-2313-8697", "clpid": "O'Callaghan-John" }, { "family_name": "Putzeys", "given_name": "Jan", "orcid": "0000-0001-8834-5852", "clpid": "Putzeys-Jan" }, { "family_name": "Raducanu", "given_name": "Bogdan C.", "orcid": "0000-0003-2207-6260", "clpid": "Raducanu-Bogdan-C" }, { "family_name": "Welkenhuysen", "given_name": "Marleen", "orcid": "0000-0001-6729-9391", "clpid": "Welkenhuysen-Marleen" }, { "family_name": "Churchland", "given_name": "Mark", "orcid": "0000-0001-9123-6526", "clpid": "Churchland-Mark" }, { "family_name": "Moore", "given_name": "Tirin", "orcid": "0000-0002-3345-2930", "clpid": "Moore-Trin" }, { "family_name": "Shadlen", "given_name": "Michael", "orcid": "0000-0002-2002-2210", "clpid": "Shadlen-Michael" }, { "family_name": "Shenoy", "given_name": "Krishna", "orcid": "0000-0003-1534-9240", "clpid": "Shenoy-Krishna" }, { "family_name": "Tsao", "given_name": "Doris", "orcid": "0000-0003-1083-1919", "clpid": "Tsao-D-Y" }, { "family_name": "Dutta", "given_name": "Barundeb", "orcid": "0000-0003-4781-9630", "clpid": "Dutta-Barundeb" }, { "family_name": "Harris", "given_name": "Timothy", "orcid": "0000-0002-6289-4439", "clpid": "Harris-Timothy-D" } ], "abstract": "
\n
\n

High-density silicon probes have transformed neuroscience by enabling large-scale neural recordings at single-cell resolution. However, existing technologies have provided limited functionality in nonhuman primates (NHPs) such as macaques. In the present report, we describe the design, fabrication and performance of Neuropixels 1.0 NHP, a high-channel electrode array designed to enable large-scale acute recording throughout large animal brains. The probe features 4,416 recording sites distributed along a 45-mm shank. Experimenters can programmably select 384 recording channels, enabling simultaneous multi-area recording from thousands of neurons with single or multiple probes. This technology substantially increases scalability and recording access relative to existing technologies and enables new classes of experiments that involve electrophysiological mapping of brain areas at single-neuron and single-spike resolution, measurement of spike–spike correlations between cells and simultaneous brain-wide recordings at scale.

\n
\n
", "doi": "10.1038/s41593-025-01976-5", "pmcid": "PMC12229894", "issn": "1097-6256", "publisher": "Nature Publishing Group", "publication": "Nature Neuroscience", "publication_date": "2025-07", "series_number": "7", "volume": "28", "issue": "7", "pages": "1562-1575" }, { "id": "authors:6ftpg-4wj22", "collection": "authors", "collection_id": "6ftpg-4wj22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211008-224633454", "type": "article", "title": "Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses", "author": [ { "family_name": "Kahan", "given_name": "Anat", "orcid": "0000-0002-4799-3017", "clpid": "Kahan-Anat" }, { "family_name": "Greenbaum", "given_name": "Alon", "orcid": "0000-0002-2897-876X", "clpid": "Greenbaum-Alon" }, { "family_name": "Jang", "given_name": "Min J.", "orcid": "0000-0002-1536-7177", "clpid": "Jang-Min-Jee" }, { "family_name": "Robinson", "given_name": "J. Elliott", "orcid": "0000-0001-9417-3938", "clpid": "Robinson-J-Elliott" }, { "family_name": "Cho", "given_name": "Jounhong Ryan", "orcid": "0000-0001-9542-716X", "clpid": "Cho-Jounhong-Ryan" }, { "family_name": "Chen", "given_name": "Xinhong", "orcid": "0000-0003-0408-0813", "clpid": "Chen-Xinhong" }, { "family_name": "Kassraian", "given_name": "Pegah", "orcid": "0000-0002-6562-7918", "clpid": "Kassraian-Fard-Pegah" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" } ], "abstract": "Optical implants to control and monitor neuronal activity in vivo have become foundational tools of neuroscience. Standard two-dimensional histology of the implant location, however, often suffers from distortion and loss during tissue processing. To address that, we developed a three-dimensional post hoc histology method called \"light-guided sectioning\" (LiGS), which preserves the tissue with its optical implant in place and allows staining and clearing of a volume up to 500 \u03bcm in depth. We demonstrate the use of LiGS to determine the precise location of an optical fiber relative to a deep brain target and to investigate the implant-tissue interface. We show accurate cell registration of ex vivo histology with single-cell, two-photon calcium imaging, obtained through gradient refractive index (GRIN) lenses, and identify subpopulations based on immunohistochemistry. LiGS provides spatial information in experimental paradigms that use optical fibers and GRIN lenses and could help increase reproducibility through identification of fiber-to-target localization and molecular profiling.", "doi": "10.1016/j.celrep.2021.109744", "pmcid": "PMC8552649", "issn": "2211-1247", "publisher": "Cell Press", "publication": "Cell Reports", "publication_date": "2021-09-28", "series_number": "13", "volume": "36", "issue": "13", "pages": "Art. No. 109744" }, { "id": "authors:hk6b4-y9189", "collection": "authors", "collection_id": "hk6b4-y9189", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200728-094010838", "type": "article", "title": "Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context", "author": [ { "family_name": "Cho", "given_name": "Jounhong Ryan", "orcid": "0000-0001-9542-716X", "clpid": "Cho-Jounhong-Ryan" }, { "family_name": "Chen", "given_name": "Xinhong", "orcid": "0000-0003-0408-0813", "clpid": "Chen-Xinhong" }, { "family_name": "Kahan", "given_name": "Anat", "orcid": "0000-0002-4799-3017", "clpid": "Kahan-Anat" }, { "family_name": "Robinson", "given_name": "J. Elliott", "orcid": "0000-0001-9417-3938", "clpid": "Robinson-J-Elliott" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" } ], "abstract": "The ability to recognize motivationally salient events and respond to them adaptively is critical for survival. Here we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process. Population recordings of DRN^(DA) neurons during associative learning tasks showed that their activity dynamically tracks salience, developing excitation to both reward- and punishment-paired cues. The DRNDA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN^(DA) activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN^(DA) neurons demonstrated that the majority of individual neurons developed activation to reward predicting cues but not to punishment-predicting cues, which was surprising and qualitatively distinct from the population results. Head-fixation during fear learning abolished the neural response to aversive cues, indicating modulation by behavioral context. Overall, these results suggest that DRN^(DA) neurons encode motivational salience, dependent on internal and external factors.", "doi": "10.1523/JNEUROSCI.2690-20.2021", "pmcid": "PMC8018733", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2021-03-24", "series_number": "12", "volume": "41", "issue": "12", "pages": "2645-2655" }, { "id": "authors:zgzy5-9p539", "collection": "authors", "collection_id": "zgzy5-9p539", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200312-124530478", "type": "article", "title": "Anatomy and activity patterns in a multifunctional motor neuron and its surrounding circuits", "author": [ { "family_name": "Ashaber", "given_name": "M\u00e1ria", "orcid": "0000-0002-5586-9585", "clpid": "Ashaber-M\u00e1ria" }, { "family_name": "Tomina", "given_name": "Yusuke", "orcid": "0000-0001-9406-1493", "clpid": "Tomina-Yusuke" }, { "family_name": "Kassraian", "given_name": "Pegah", "orcid": "0000-0002-6562-7918", "clpid": "Kassraian-Fard-Pegah" }, { "family_name": "Bushong", "given_name": "Eric A.", "orcid": "0000-0001-6195-2433", "clpid": "Bushong-Eric-A" }, { "family_name": "Kristan", "given_name": "William B.", "clpid": "Kristan-William-B-Jr." }, { "family_name": "Ellisman", "given_name": "Mark H.", "orcid": "0000-0001-8893-8455", "clpid": "Ellisman-Mark-H" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Dorsal Excitor motor neuron DE-3 in the medicinal leech plays three very different dynamical roles in three different behaviors. Without rewiring its anatomical connectivity, how can a motor neuron dynamically switch roles to play appropriate roles in various behaviors? We previously used voltage-sensitive dye imaging to record from DE-3 and most other neurons in the leech segmental ganglion during (fictive) swimming, crawling, and local-bend escape (Tomina and Wagenaar, 2017). Here, we repeated that experiment, then re-imaged the same ganglion using serial blockface electron microscopy and traced DE-3's processes. Further, we traced back the processes of DE-3's presynaptic partners to their respective somata. This allowed us to analyze the relationship between circuit anatomy and the activity patterns it sustains. We found that input synapses important for all the behaviors were widely distributed over DE-3's branches, yet that functional clusters were different during (fictive) swimming vs. crawling.", "doi": "10.7554/eLife.61881", "issn": "2050-084X", "publisher": "eLife Sciences Publications", "publication": "eLife", "publication_date": "2021-02-15", "volume": "10", "pages": "Art. No. e61881" }, { "id": "authors:70esk-xma64", "collection": "authors", "collection_id": "70esk-xma64", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191017-074022753", "type": "article", "title": "Stimulus-specific hypothalamic encoding of a persistent defensive state", "author": [ { "family_name": "Kennedy", "given_name": "Ann", "orcid": "0000-0002-3782-0518", "clpid": "Kennedy-Ann" }, { "family_name": "Kunwar", "given_name": "Prabhat S.", "clpid": "Kunwar-Prabhat-S" }, { "family_name": "Li", "given_name": "Ling-yun", "clpid": "Li-Ling-yun" }, { "family_name": "Stagkourakis", "given_name": "Stefanos", "orcid": "0000-0003-1218-791X", "clpid": "Stagkourakis-Stefanos" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "abstract": "Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial hypothalamus (VMHdm/c) that express the nuclear receptor protein NR5A1 (also known as SF1) are necessary for defensive responses to predators in mice. Optogenetic activation of these neurons, referred to here as VMHdm^(SF1) neurons, elicits defensive behaviours that outlast stimulation, which suggests the induction of a persistent internal state of fear or anxiety. Here we show that in response to naturalistic threatening stimuli, VMHdm^(SF1) neurons in mice exhibit activity that lasts for many tens of seconds. This persistent activity was correlated with, and required for, persistent defensive behaviour in an open-field assay, and depended on neurotransmitter release from VMHdm^(SF1) neurons. Stimulation and calcium imaging in acute slices showed that there is local excitatory connectivity between VMHdm^(SF1) neurons. Microendoscopic calcium imaging of VMHdm^(SF1) neurons revealed that persistent activity at the population level reflects heterogeneous dynamics among individual cells. Unexpectedly, distinct but overlapping VMHdm^(SF1) subpopulations were persistently activated by different modalities of threatening stimulus. Computational modelling suggests that neither recurrent excitation nor slow-acting neuromodulators alone can account for persistent activity that maintains stimulus identity. Our results show that stimulus-specific slow neural dynamics in the hypothalamus, on a time scale orders of magnitude longer than that of working memory in the cortex, contribute to a persistent emotional state.", "doi": "10.1038/s41586-020-2728-4", "pmcid": "PMC7606611", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2020-10-29", "series_number": "7831", "volume": "586", "issue": "7831", "pages": "730-734" }, { "id": "authors:qxsmb-0bw43", "collection": "authors", "collection_id": "qxsmb-0bw43", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201030-151256559", "type": "article", "title": "Label-free imaging of lipid-rich biological tissues by mid-infrared photoacoustic microscopy", "author": [ { "family_name": "He", "given_name": "Yun", "orcid": "0000-0001-8430-6370", "clpid": "He-Yun" }, { "family_name": "Shi", "given_name": "Junhui", "orcid": "0000-0002-5741-2781", "clpid": "Shi-Junhui" }, { "family_name": "Pleitez", "given_name": "Miguel A.", "clpid": "Pleitez-M-A" }, { "family_name": "Maslov", "given_name": "Konstantin", "orcid": "0000-0003-3408-8840", "clpid": "Maslov-K-I" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Wang", "given_name": "Lihong V.", "orcid": "0000-0001-9783-4383", "clpid": "Wang-Lihong-V" } ], "abstract": "Significance: Mid-infrared (IR) imaging based on the vibrational transition of biomolecules provides good chemical-specific contrast in label-free imaging of biology tissues, making it a popular tool in both biomedical studies and clinical applications. However, the current technology typically requires thin and dried or extremely flat samples, whose complicated processing limits this technology's broader translation. \n\nAim: To address this issue, we report mid-IR photoacoustic microscopy (PAM), which can readily work with fresh and thick tissue samples, even when they have rough surfaces.\nApproach: We developed a transmission-mode mid-IR PAM system employing an optical parametric oscillation laser operating in the wavelength range from 2.5 to 12\u2009\u03bcm. Due to its high sensitivity to optical absorption and the low ultrasonic attenuation of tissue, our PAM achieved greater probing depth than Fourier transform IR spectroscopy, thus enabling imaging fresh and thick tissue samples with rough surfaces.\nResults: In our spectroscopy study, the CH\u2082 symmetric stretching at 2850\u2009\u2009cm\u207b\u00b9 (3508 nm) was found to be an excellent source of endogenous contrast for lipids. At this wavenumber, we demonstrated label-free imaging of the lipid composition in fresh, manually cut, and unprocessed tissue sections of up to 3-mm thickness. \n\nConclusions: Our technology requires no time-consuming sample preparation procedure and has great potential in both fast clinical histological analysis and fundamental biological studies.", "doi": "10.1117/1.jbo.25.10.106506", "issn": "1083-3668", "publisher": "Society of Photo-Optical Instrumentation Engineers", "publication": "Journal of Biomedical Optics", "publication_date": "2020-10-28", "series_number": "10", "volume": "25", "issue": "10", "pages": "Art. No. 106506" }, { "id": "authors:16ywz-0cj69", "collection": "authors", "collection_id": "16ywz-0cj69", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190219-112051503", "type": "article", "title": "Electrophysiology and transcriptomics reveal two photoreceptor classes and complex visual integration in Hirudo verbana", "author": [ { "family_name": "Stowasser", "given_name": "Annette", "clpid": "Stowasser-A" }, { "family_name": "Stahl", "given_name": "Aaron", "clpid": "Stahl-A" }, { "family_name": "Benoit", "given_name": "Joshua B.", "clpid": "Benoit-J-B" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Among animals with visual processing mechanisms, the leech Hirudo verbana is a rare example in which all neurons can be identified. However, little is known about its visual system, which is composed of several pigmented head eyes and photosensitive non-pigmented sensilla that are distributed across its entire body. Although several interneurons are known to respond to visual stimuli, their response properties are poorly understood. Among these, the S-cell system is especially intriguing: it is multimodal, spans the entire body of the leech and is thought to be involved in sensory integration. To improve our understanding of the role of this system, we tested its spectral sensitivity, spatial integration and adaptation properties. The response of the S-cell system to visual stimuli was found to be strongly dependent on the size of the area stimulated, and adaptation was local. Furthermore, an adaptation experiment demonstrated that at least two color channels contributed to the response, and that their contribution was dependent on the adaptation to the background. The existence of at least two color channels was further supported by transcriptomic evidence, which indicated the existence of at least two distinct groups of putative opsins for leeches. Taken together, our results show that the S-cell system has response properties that could be involved in the processing of spatial and color information of visual stimuli. We propose the leech as a novel system to understand visual processing mechanisms with many practical advantages.", "doi": "10.1242/jeb.201764", "pmcid": "PMC6703701", "issn": "0022-0949", "publisher": "Company of Biologists", "publication": "Journal of Experimental Biology", "publication_date": "2019-08", "series_number": "15", "volume": "222", "issue": "15", "pages": "Art. No. jeb201764" }, { "id": "authors:3ngwx-46089", "collection": "authors", "collection_id": "3ngwx-46089", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180717-145659939", "type": "article", "title": "Two-photon microscopy with a double-wavelength metasurface objective lens", "author": [ { "family_name": "Arbabi", "given_name": "Ehsan", "orcid": "0000-0002-5328-3863", "clpid": "Arbabi-E" }, { "family_name": "Li", "given_name": "Jiaqi", "orcid": "0000-0003-2021-2310", "clpid": "Li-Jiaqi" }, { "family_name": "Hutchins", "given_name": "Romanus J.", "clpid": "Hutchins-R-J" }, { "family_name": "Kamali", "given_name": "Seyedeh Mahsa", "orcid": "0000-0002-6968-811X", "clpid": "Kamali-S-M" }, { "family_name": "Arbabi", "given_name": "Amir", "orcid": "0000-0001-8831-7552", "clpid": "Arbabi-A" }, { "family_name": "Horie", "given_name": "Yu", "orcid": "0000-0001-7083-1270", "clpid": "Horie-Yu" }, { "family_name": "Van Dorpe", "given_name": "Pol", "clpid": "Van-Dorpe-P" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Faraon", "given_name": "Andrei", "orcid": "0000-0002-8141-391X", "clpid": "Faraon-A" } ], "abstract": "Two-photon microscopy is a key imaging technique in life sciences due to its superior deep-tissue imaging capabilities. Light-weight and compact two-photon microscopes are of great interest because of their applications for in vivo deep brain imaging. Recently, dielectric metasurfaces have enabled a new category of small and lightweight optical elements, including objective lenses. Here we experimentally demonstrate two-photon microscopy using a double-wavelength metasurface lens. It is specifically designed to focus 820 and 605 nm light, corresponding to the excitation and emission wavelengths of the measured fluorophors, to the same focal distance. The captured two-photon images are qualitatively comparable to the ones taken by a conventional objective lens. Our metasurface lens can enable ultracompact two-photon microscopes with similar performance compared to current systems that are usually based on graded-index-lenses. In addition, further development of tunable metasurface lenses will enable fast axial scanning for volumetric imaging.", "doi": "10.1021/acs.nanolett.8b01737", "issn": "1530-6984", "publisher": "American Chemical Society", "publication": "Nano Letters", "publication_date": "2018-08-08", "series_number": "8", "volume": "18", "issue": "8", "pages": "4943-4948" }, { "id": "authors:p8s3m-bv811", "collection": "authors", "collection_id": "p8s3m-bv811", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180402-075326031", "type": "article", "title": "Dual-sided Voltage-sensitive Dye Imaging of Leech Ganglia", "author": [ { "family_name": "Tomina", "given_name": "Yusuke", "orcid": "0000-0001-9406-1493", "clpid": "Tomina-Yusuke" }, { "family_name": "Wagenaar", "given_name": "Daniel", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "In this protocol, we introduce an effective method for voltage-sensitive dye (VSD) loading and imaging of leech ganglia as used in Tomina and Wagenaar (2017). Dissection and dye loading procedures are the most critical steps toward successful whole-ganglion VSD imaging. The former entails the removal of the sheath that covers neurons in the segmental ganglion of the leech, which is required for successful dye loading. The latter entails gently flowing a new generation VSD, VF2.1(OMe).H, onto both sides of the ganglion simultaneously using a pair of peristaltic pumps. We expect the described techniques to translate broadly to wide-field VSD imaging in other thin and relatively transparent nervous systems.", "doi": "10.21769/BioProtoc.2751", "pmcid": "PMC5867905", "issn": "2331-8325", "publisher": "Bio-Protocol", "publication": "Bio-protocol", "publication_date": "2018-03-05", "series_number": "5", "volume": "8", "issue": "5", "pages": "Art. No. e2751" }, { "id": "authors:rh132-fa824", "collection": "authors", "collection_id": "rh132-fa824", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180227-093930741", "type": "article", "title": "Responses to mechanically and visually cued water waves in the nervous system of the medicinal leech", "author": [ { "family_name": "Lehmkuhl", "given_name": "Andrew M.", "orcid": "0000-0002-5712-2012", "clpid": "Lehmkuhl-Andrew-M" }, { "family_name": "Muthusamy", "given_name": "Arunkumar", "orcid": "0000-0002-1804-586X", "clpid": "Muthusamy-Arunkumar" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Sensitivity to water waves is a key modality by which aquatic predators can detect and localize their prey. For one such predator \u2013 the medicinal leech, Hirudo verbana \u2013 behavioral responses to visual and mechanical cues from water waves are well documented. Here, we quantitatively characterized the response patterns of a multisensory interneuron, the S cell, to mechanically and visually cued water waves. As a function of frequency, the response profile of the S cell replicated key features of the behavioral prey localization profile in both visual and mechanical modalities. In terms of overall firing rate, the S cell response was not direction selective, and although the direction of spike propagation within the S cell system did follow the direction of wave propagation under certain circumstances, it is unlikely that downstream neuronal targets can use this information. Accordingly, we propose a role for the S cell in the detection of waves but not in the localization of their source. We demonstrated that neither the head brain nor the tail brain are required for the S cell to respond to visually cued water waves.", "doi": "10.1242/jeb.171728", "pmcid": "PMC5868928", "issn": "0022-0949", "publisher": "Company of Biologists", "publication": "Journal of Experimental Biology", "publication_date": "2018-02-22", "series_number": "4", "volume": "221", "issue": "4", "pages": "Art. No. jeb171728" }, { "id": "authors:j63et-aw064", "collection": "authors", "collection_id": "j63et-aw064", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171009-132459678", "type": "article", "title": "A double-sided microscope to realize whole-ganglion imaging of membrane potential in the medicinal leech", "author": [ { "family_name": "Tomina", "given_name": "Yusuke", "orcid": "0000-0001-9406-1493", "clpid": "Tomina-Yusuke" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Studies of neuronal network emergence during sensory processing and motor control are greatly facilitated by technologies that allow us to simultaneously record the membrane potential dynamics of a large population of neurons in single cell resolution. To achieve whole-brain recording with the ability to detect both small synaptic potentials and action potentials, we developed a voltage-sensitive dye (VSD) imaging technique based on a double-sided microscope that can image two sides of a nervous system simultaneously. We applied this system to the segmental ganglia of the medicinal leech. Double-sided VSD imaging enabled simultaneous recording of membrane potential events from almost all of the identifiable neurons. Using data obtained from double-sided VSD imaging, we analyzed neuronal dynamics in both sensory processing and generation of behavior and constructed functional maps for identification of neurons contributing to these processes.", "doi": "10.7554/eLife.29839", "pmcid": "PMC5656430", "issn": "2050-084X", "publisher": "eLife Sciences Publications", "publication": "eLife", "publication_date": "2017-09-25", "volume": "6", "pages": "Art. No. e29839" }, { "id": "authors:cqwf8-5ca47", "collection": "authors", "collection_id": "cqwf8-5ca47", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151109-105331416", "type": "article", "title": "Optically transparent multi-suction electrode arrays", "author": [ { "family_name": "Nagarah", "given_name": "John M.", "clpid": "Nagarah-J-M" }, { "family_name": "Stowasser", "given_name": "Annette", "clpid": "Stowasser-A" }, { "family_name": "Parker", "given_name": "Rell L.", "clpid": "Parker-R-L" }, { "family_name": "Asari", "given_name": "Hiroki", "clpid": "Asari-H" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Multielectrode arrays (MEAs) allow for acquisition of multisite electrophysiological activity with submillisecond temporal resolution from neural preparations. The signal to noise ratio from such arrays has recently been improved by substrate perforations that allow negative pressure to be applied to the tissue; however, such arrays are not optically transparent, limiting their potential to be combined with optical-based technologies. We present here multi-suction electrode arrays (MSEAs) in quartz that yield a substantial increase in the detected number of units and in signal to noise ratio from mouse cortico-hippocampal slices and mouse retina explants. This enables the visualization of stronger cross correlations between the firing rates of the various sources. Additionally, the MSEA's transparency allows us to record voltage sensitive dye activity from a leech ganglion with single neuron resolution using widefield microscopy simultaneously with the electrode array recordings. The combination of enhanced electrical signals and compatibility with optical-based technologies should make the MSEA a valuable tool for investigating neuronal circuits.", "doi": "10.3389/fnins.2015.00384", "pmcid": "PMC4611137", "issn": "1662-453X", "publisher": "Frontiers", "publication": "Frontiers in Neuroscience", "publication_date": "2015-10-20", "volume": "9", "pages": "Art. No. 384" }, { "id": "authors:pa3k2-5p382", "collection": "authors", "collection_id": "pa3k2-5p382", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150313-092545773", "type": "article", "title": "Responses to Conflicting Stimuli in a Simple Stimulus\u2013Response Pathway", "author": [ { "family_name": "Baljon", "given_name": "Pieter Laurens", "clpid": "Baljon-P-L" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "The \"local bend response\" of the medicinal leech (Hirudo verbana) is a stimulus\u2013response pathway that enables the animal to bend away from a pressure stimulus applied anywhere along its body. The neuronal circuitry that supports this behavior has been well described, and its responses to individual stimuli are understood in quantitative detail. We probed the local bend system with pairs of electrical stimuli to sensory neurons that could not logically be interpreted as a single touch to the body wall and used multiple suction electrodes to record simultaneously the responses in large numbers of motor neurons. In all cases, responses lasted much longer than the stimuli that triggered them, implying the presence of some form of positive feedback loop to sustain the response. When stimuli were delivered simultaneously, the resulting motor neuron output could be described as an evenly weighted linear combination of the responses to the constituent stimuli. However, when stimuli were delivered sequentially, the second stimulus had greater impact on the motor neuron output, implying that the positive feedback in the system is not strong enough to render it immune to further input.", "doi": "10.1523/JNEUROSCI.3823-14.2015", "pmcid": "PMC4323524", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2015-02-11", "series_number": "6", "volume": "35", "issue": "6", "pages": "2398-2406" }, { "id": "authors:hn7fp-qp783", "collection": "authors", "collection_id": "hn7fp-qp783", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140820-140703376", "type": "article", "title": "Effects of millimeter wave irradiation and equivalent thermal heating on the activity of individual neurons in the leech ganglion", "author": [ { "family_name": "Romanenko", "given_name": "Sergii", "clpid": "Romanenko-S" }, { "family_name": "Siegel", "given_name": "Peter H.", "orcid": "0000-0002-2539-4646", "clpid": "Siegel-P-H" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Pikov", "given_name": "Victor", "clpid": "Pikov-V" } ], "abstract": "Many of today's radiofrequency-emitting devices in telecommunication, telemedicine, transportation safety, and security/military applications use the millimeter-wave (MMW) band (30-300 GHz). To evaluate the biological safety and possible applications of this radiofrequency band for neuroscience and neurology, we have investigated the physiological effects of low-intensity 60 GHz electromagnetic irradiation on individual neurons in the leech midbody ganglia. We applied incident power densities of 1, 2, and 4 mW/cm^2 to the whole ganglion for a period of 1 minute, while recording the action potential with a standard sharp-electrode electrophysiology setup. For comparison, the recognized U.S. safe exposure limit is 1 mW/cm^2 for 6 minutes. During the exposure to MMWs and gradual bath heating at a rate of 0.04 \u00baC/sec (2.4 \u00baC/min), the ganglionic neurons exhibited similar dose-dependent hyperpolarization of the plasma membrane and decrease in the action potential amplitude. However, narrowing of the action potential half-width during MMW irradiation at 4 mW/cm^2 was 5 times more pronounced, as compared to equivalent bath heating of 0.6 \u00baC. Even more dramatic difference in the effects of MMW irradiation and bath heating was on the firing rate, which was suppressed at all applied MMW power densities and was increased in a dose-dependent manner during gradual bath heating. The mechanism of enhanced narrowing of action potentials and suppressed firing by MMW irradiation, as compared to gradual bath heating, is hypothesized to involve specific coupling of MMW energy with the neuronal plasma membrane.", "doi": "10.1152/jn.00357.2014", "pmcid": "PMC4233276", "issn": "0022-3077", "publisher": "American Physiological Society", "publication": "Journal of Neurophysiology", "publication_date": "2014-11-15", "series_number": "10", "volume": "112", "issue": "10", "pages": "2423-2431" }, { "id": "authors:1h1ew-94k46", "collection": "authors", "collection_id": "1h1ew-94k46", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140710-080237054", "type": "article", "title": "Transparent Multi-Suction Electrode Arrays for in vitro Neural Network Investigations", "author": [ { "family_name": "Nagarah", "given_name": "John M.", "clpid": "Nagarah-J-M" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Large-scale multisite electrophysiology recordings with high temporal resolution\nare essential to discover neural circuitry and elucidate their structurefunction\nrelationship. We contribute to this effort by combining multielectrode\narrays (MEAs) with through pore arrays in quartz substrates to create multisuction\nelectrode arrays. The MEA allows for multisite extracellular recordings\nfrom neural tissue while the through pore array permits suction to be applied to\nthe tissue to form more intimate contact with the electrodes. We successfully\nrecorded from mouse hippocampi, mouse retina, and leech segmental ganglia.\nHippocampus and retina tissue show at least a 50% increase in S/N and twofold\nincrease in detectable spikes following suction. (Interestingly, spiking activity\nand S/N of spikes in leech ganglia mostly do not increase after applied suction,\nsuggesting sources deeper in the tissue.) Finally, we demonstrate optical imaging\nthrough the transparent substrate to visualize the neurons at the electrode\ninterface simultaneously with electrophysiology recordings. This technology\nwill facilitate the combination of optical-based measurements such as\nvoltage-sensitive dye imaging with multisite electrophysiological recordings\nwith high temporal resolution of neuronal networks in a wide range of vertebrate\nand invertebrate preparations, at the single spike level.", "doi": "10.1016/j.bpj.2013.11.2346", "issn": "0006-3495", "publisher": "Biophysical Society", "publication": "Biophysical Journal", "publication_date": "2014-01-28", "series_number": "2", "volume": "106", "issue": "2", "pages": "417A" }, { "id": "authors:kejhn-02471", "collection": "authors", "collection_id": "kejhn-02471", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130606-100422173", "type": "article", "title": "Discontinuous locomotion and prey sensing in the leech", "author": [ { "family_name": "Harley", "given_name": "Cynthia M.", "clpid": "Harley-Cynthia-M" }, { "family_name": "Rossi", "given_name": "Matthew", "clpid": "Rossi-Matthew" }, { "family_name": "Cienfuegos", "given_name": "Javier", "clpid": "Cienfuegos-Javier" }, { "family_name": "Wagenaar", "given_name": "Daniel", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "The medicinal leech, Hirudo verbana, is an aquatic predator that utilizes water waves to locate its prey. However, to reach their prey, the leeches must move within the same water that they are using to sense prey. This requires that they either move ballistically towards a pre-determined prey location or that they account for their self-movement and continually track prey. We found that leeches do not localize prey ballistically. Instead, they require continual sensory information to track their prey. Indeed, in the event that the prey moves, leeches will approach the prey's new location. While leeches need to continually sense water disturbances to update their percept of prey location, their own behavior is discontinuous \u2013 approaching prey involves switching between swimming, crawling and non-locomoting. Each of these behaviors may allow for different sensory capabilities and may require different sensory filters. Here, we examined the sensory capabilities of leeches during each of these behaviors. We found that while one could expect the non-locomoting phases to direct subsequent behaviors, crawling phases were more effective than non-locomotor phases for providing direction. During crawling bouts, leeches adjusted their heading so as to become more directed towards the stimulus. This was not observed during swimming. Furthermore, in the presence of prey-like stimuli, leeches crawled more often and for longer periods of time.", "doi": "10.1242/jeb.075911", "issn": "0022-0949", "publisher": "Company of Biologists", "publication": "Journal of Experimental Biology", "publication_date": "2013-05-15", "series_number": "10", "volume": "216", "issue": "10", "pages": "1890-1897" }, { "id": "authors:0hk4a-42582", "collection": "authors", "collection_id": "0hk4a-42582", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120416-142037502", "type": "article", "title": "Ultradeep fused silica glass etching with an HF-resistant photosensitive resist for optical imaging applications", "author": [ { "family_name": "Nagarah", "given_name": "John M.", "clpid": "Nagarah-J-M" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Microfluidic and optical sensing platforms are commonly fabricated in glass and fused silica (quartz) because of their optical transparency and chemical inertness. Hydrofluoric acid (HF) solutions are the etching media of choice for deep etching into silicon dioxide substrates, but processing schemes become complicated and expensive for etching times greater than 1 h due to the aggressiveness of HF migration through most masking materials. We present here etching into fused silica more than 600 \u00b5m deep while keeping the substrate free of pits and maintaining a polished etched surface suitable for biological imaging. We utilize an HF-resistant photosensitive resist (HFPR) which is not attacked in 49% HF solution. Etching characteristics are compared for substrates masked with the HFPR alone and the HFPR patterned on top of Cr/Au and polysilicon masks. We used this etching process to fabricate suspended fused silica membranes, 8\u201316 \u00b5m thick, and show that imaging through the membranes does not negatively affect image quality of fluorescence microscopy of biological tissue. Finally, we realize small through-pore arrays in the suspended membranes. Such devices will have applications in planar electrophysiology platforms, especially where optical imaging is required.", "doi": "10.1088/0960-1317/22/3/035011", "issn": "0960-1317", "publisher": "IOP", "publication": "Journal of Micromechanics and Microengineering", "publication_date": "2012-03", "series_number": "3", "volume": "22", "issue": "3", "pages": "Art. No. 035011" }, { "id": "authors:k56hx-vqt07", "collection": "authors", "collection_id": "k56hx-vqt07", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120410-144819396", "type": "article", "title": "An Optically Stabilized Fast-Switching Light Emitting Diode as a Light Source for Functional Neuroimaging", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Neuroscience research increasingly relies on optical methods for evoking neuronal activity as well as for measuring it, making bright and stable light sources critical building blocks of modern experimental setups. This paper presents a method to control the brightness of a high-power light emitting diode (LED) light source to an unprecedented level of stability. By continuously monitoring the actual light output of the LED with a photodiode and feeding the result back to the LED's driver by way of a proportional-integral controller, drift was reduced to as little as 0.007% per hour over a 12-h period, and short-term fluctuations to 0.005% root-mean-square over 10 seconds. The LED can be switched on and off completely within 100 \u00b5s, a feature that is crucial when visual stimuli and light for optical recording need to be interleaved to obtain artifact-free recordings. The utility of the system is demonstrated by recording visual responses in the central nervous system of the medicinal leech Hirudo verbana using voltage-sensitive dyes.", "doi": "10.1371/journal.pone.0029822", "pmcid": "PMC3253093", "issn": "1932-6203", "publisher": "Public Library of Science", "publication": "PLoS ONE", "publication_date": "2012-01-06", "series_number": "1", "volume": "7", "issue": "1", "pages": "Art. No. e29822" }, { "id": "authors:1bhp1-ztn48", "collection": "authors", "collection_id": "1bhp1-ztn48", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111129-104156137", "type": "article", "title": "Developmentally regulated multisensory integration for prey localization in the medicinal leech", "author": [ { "family_name": "Harley", "given_name": "Cynthia M.", "clpid": "Harley-C-M" }, { "family_name": "Cienfuegos", "given_name": "Javier", "clpid": "Cienfuegos-J" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" } ], "abstract": "Medicinal leeches, like many aquatic animals, use water disturbances to localize their prey, so they need to be able to determine if a wave disturbance is created by prey or by another source. Many aquatic predators perform this separation by responding only to those wave frequencies representing their prey. As leeches' prey preference changes over the course of their development, we examined their responses at three different life stages. We found that juveniles more readily localize wave sources of lower frequencies (2 Hz) than their adult counterparts (8\u201312 Hz), and that adolescents exhibited elements of both juvenile and adult behavior, readily localizing sources of both frequencies. Leeches are known to be able to localize the source of waves through the use of either mechanical or visual information. We separately characterized their ability to localize various frequencies of stimuli using unimodal cues. Within a single modality, the frequency\u2013response curves of adults and juveniles were virtually indistinguishable. However, the differences between the responses for each modality (visual and mechanosensory) were striking. The optimal visual stimulus had a much lower frequency (2 Hz) than the optimal mechanical stimulus (12 Hz). These frequencies matched, respectively, the juvenile and the adult preferred frequency for multimodally sensed waves. This suggests that, in the multimodal condition, adult behavior is driven more by mechanosensory information and juvenile behavior more by visual. Indeed, when stimuli of the two modalities were placed in conflict with one another, adult leeches, unlike juveniles, were attracted to the mechanical stimulus much more strongly than to the visual stimulus.", "doi": "10.1242/jeb.059618", "issn": "0022-0949", "publisher": "Company of Biologists", "publication": "Journal of Experimental Biology", "publication_date": "2011-11", "series_number": "22", "volume": "214", "issue": "22", "pages": "3801-3807" }, { "id": "authors:fzfr2-21071", "collection": "authors", "collection_id": "fzfr2-21071", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101028-094759611", "type": "article", "title": "Alpha-conotoxin ImI disrupts central control of swimming in the medicinal leech", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Gonzalez", "given_name": "Ruben", "clpid": "Gonzalez-R" }, { "family_name": "Ries", "given_name": "David C.", "clpid": "Ries-D-C" }, { "family_name": "Kristan", "given_name": "Wiliam B., Jr.", "clpid": "Kristan-W-B" }, { "family_name": "French", "given_name": "Kathleen A.", "clpid": "French-K-A" } ], "abstract": "Medicinal leeches (Hirudo spp.) swim using a metachronal, front-to-back undulation. The behavior is generated by central pattern generators (CPGs) distributed along the animal's midbody ganglia and is coordinated by both central and peripheral mechanisms. Here we report that a component of the venom of Conus imperialis, \u03b1-conotoxin ImI, known to block nicotinic acetyl-choline receptors in other species,\ndisrupts swimming. Leeches injected with the toxin swam in circles with exaggerated dorsoventral bends and reduced forward velocity. Fictive swimming in isolated nerve cords was even more strongly disrupted, indicating that the toxin targets the CPGs and central coordination, while peripheral coordination partially rescues the behavior in intact animals.", "doi": "10.1016/j.neulet.2010.08.078", "pmcid": "PMC2956871", "issn": "0304-3940", "publisher": "Elsevier", "publication": "Neuroscience Letters", "publication_date": "2010-11-26", "series_number": "3", "volume": "485", "issue": "3", "pages": "151-156" }, { "id": "authors:x15dn-8kd85", "collection": "authors", "collection_id": "x15dn-8kd85", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100412-080058326", "type": "article", "title": "A Hormone-Activated Central Pattern Generator for Courtship", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Hamilton", "given_name": "M. Sarhas", "clpid": "Hamilton-M-S" }, { "family_name": "Huang", "given_name": "Tracy", "clpid": "Huang-Tracy" }, { "family_name": "Kristan", "given_name": "William B.", "clpid": "Kristan-W-B" }, { "family_name": "French", "given_name": "Kathleen A.", "clpid": "French-K-A" } ], "abstract": "Background:\nMedicinal leeches (Hirudo spp.) are simultaneous hermaphrodites. Mating occurs after a stereotyped twisting and oral exploration that result in the alignment of the male and/or female gonopores of one leech with the complementary gonopores of a partner. The neural basis of this behavior is presently unknown and currently impossible to study directly because electrophysiological recording techniques disrupt the behavior.\nResults:\nHere we report that (Arg^8)-conopressin G and two other members of the oxytocin/vasopressin family of peptide hormones induce in Hirudo verbana a sequence of behaviors that closely mimic elements of spontaneous reproductive behavior. Through a series of progressively more reduced preparations, we show that one of these behaviors, a stereotyped twisting that is instrumental in aligning gonopores in preparation for copulation, is the product of a central pattern generator that consists of oscillators in ganglia M5 and M6 (the ganglia in the reproductive segments of the leech), and also in ganglion M4, which was not previously known to play a role in reproductive behavior. We find that the behavior is periodic, with a remarkably long cycle period of around five minutes, placing it among the slowest behavioral rhythms (other than diurnal and annual rhythms) yet described.\nConclusion: \nThese results establish the leech as a new model system for studying aspects of the neuronal basis of reproductive behavior.\nHighlights: \n\nOxytocin/vasopressin homologs induce precopulatory movements in a leech. These movements are generated by a central pattern generator. Segmental ganglia M4, M5, and M6 can each generate fictive behavior in isolation", "doi": "10.1016/j.cub.2010.02.027", "pmcid": "PMC2858972", "issn": "0960-9822", "publisher": "Cell Press", "publication": "Current Biology", "publication_date": "2010-03-23", "series_number": "6", "volume": "20", "issue": "6", "pages": "487-495" }, { "id": "authors:y3g4g-42354", "collection": "authors", "collection_id": "y3g4g-42354", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100514-100202108", "type": "article", "title": "Automated Video Analysis of Animal Movements Using Gabor Orientation Filters", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Kristan", "given_name": "Wiliam B., Jr.", "clpid": "Kristan-W-B-Jr" } ], "abstract": "To quantify locomotory behavior, tools for determining the location and shape of an animal's body are a first requirement. Video recording is a convenient technology to store raw movement data, but extracting body coordinates from video recordings is a nontrivial task. The algorithm described in this paper solves this task for videos of leeches or other quasi-linear animals in a manner inspired by the mammalian visual processing system: the video frames are fed through a bank of Gabor filters, which locally detect segments of the animal at a particular orientation. The algorithm assumes that the image location with maximal filter output lies on the animal's body and traces its shape out in both directions from there. The algorithm successfully extracted location and shape information from video clips of swimming leeches, as well as from still photographs of swimming and crawling snakes. A Matlab implementation with a graphical user interface is available online, and should make this algorithm conveniently usable in many other contexts.", "doi": "10.1007/s12021-010-9062-1", "pmcid": "PMC2841272", "issn": "1539-2791", "publisher": "Humana Press Inc.", "publication": "Neuroinformatics", "publication_date": "2010-03", "series_number": "1", "volume": "8", "issue": "1", "pages": "33-42" }, { "id": "authors:dscam-eeg20", "collection": "authors", "collection_id": "dscam-eeg20", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WAGjnrb06", "type": "article", "title": "Searching for plasticity in dissociated cortical cultures on multi-electrode arrays", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Pine", "given_name": "Jerome", "clpid": "Pine-J" }, { "family_name": "Potter", "given_name": "Steve M.", "clpid": "Potter-S-M" } ], "abstract": "We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using distributed electrical stimulation.", "doi": "10.1186/1477-5751-5-16", "pmcid": "PMC1800351", "issn": "1477-5751", "publisher": "BioMed Central", "publication": "Journal of Negative Results in BioMedicine", "publication_date": "2006-10-26", "volume": "5", "pages": "Art. No. 16" }, { "id": "authors:1dtz8-e5h52", "collection": "authors", "collection_id": "1dtz8-e5h52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WAGpre06", "type": "article", "title": "Persistent dynamic attractors in activity patterns of cultured neuronal networks", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "N\u00e1dasdy", "given_name": "Zoltan", "clpid": "N\u00e1dasdy-Z" }, { "family_name": "Potter", "given_name": "Steve M.", "clpid": "Potter-S-M" } ], "abstract": "Three remarkable features of the nervous system\u2014complex spatiotemporal patterns, oscillations, and persistent activity\u2014are fundamental to such diverse functions as stereotypical motor behavior, working memory, and awareness. Here we report that cultured cortical networks spontaneously generate a hierarchical structure of periodic activity with a strongly stereotyped population-wide spatiotemporal structure demonstrating all three fundamental properties in a recurring pattern. During these \"superbursts,\" the firing sequence of the culture periodically converges to a dynamic attractor orbit. Precursors of oscillations and persistent activity have previously been reported as intrinsic properties of the neurons. However, complex spatiotemporal patterns that are coordinated in a large population of neurons and persist over several hours\u2014and thus are capable of representing and preserving information\u2014cannot be explained by known oscillatory properties of isolated neurons. Instead, the complexity of the observed spatiotemporal patterns implies large-scale self-organization of neurons interacting in a precise temporal order even in vitro, in cultures usually considered to have random connectivity.", "doi": "10.1103/PhysRevE.73.051907", "pmcid": "PMC2570189", "issn": "1539-3755", "publisher": "American Physical Society", "publication": "Physical Review E", "publication_date": "2006-05", "series_number": "5", "volume": "73", "issue": "5", "pages": "Art. No. 051907" }, { "id": "authors:s7m4b-tf846", "collection": "authors", "collection_id": "s7m4b-tf846", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WAGbmcn06", "type": "article", "title": "An extremely rich repertoire of bursting patterns during the development of cortical cultures", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Pine", "given_name": "Jerome", "clpid": "Pine-J" }, { "family_name": "Potter", "given_name": "Steve M.", "clpid": "Potter-S-M" } ], "abstract": "Background: We have collected a comprehensive set of multi-unit data on dissociated cortical cultures. Previous studies of the development of the electrical activity of dissociated cultures of cortical neurons each focused on limited aspects of its dynamics, and were often based on small numbers of observed cultures. We followed 58 cultures of different densities---3000 to 50,000 neurons on areas of 30 to 75 mm^2---growing on multi-electrode arrays (MEAs) during the first five weeks of their development. \n\nResults: Plating density had a profound effect on development. While the aggregate spike detection rate scaled linearly with density, as expected from the number of cells in proximity to electrodes, dense cultures started to exhibit bursting behavior earlier in development than sparser cultures. Analysis of responses to electrical stimulation suggests that axonal outgrowth likewise occurred faster in dense cultures. After two weeks, the network activity was dominated by population bursts in most cultures. In contrast to previous reports, development continued with changing burst patterns throughout the observation period. Burst patterns were extremely varied, with inter-burst intervals between 1 and 300 s, different amounts of temporal clustering of bursts, and different firing rate profiles during bursts. During certain stages of development bursts were organized into tight clusters with highly conserved internal structure. \n\nConclusions: Dissociated cultures of cortical cells exhibited a much richer repertoire of activity patterns than previously reported. Except for the very sparsest cultures, all cultures exhibited globally synchronized bursts, but bursting patterns changed over the course of development, and varied considerably between preparations. This emphasizes the importance of using multiple preparations---not just multiple cultures from one preparation---in any study involving neuronal cultures. These results are based on 963 half-hour-long recordings. To encourage further investigation of the rich range of behaviors exhibited by cortical cells in vitro, we are making the data available to other researchers, together with Matlab code to facilitate access.", "doi": "10.1186/1471-2202-7-11", "pmcid": "PMC1420316", "issn": "1471-2202", "publisher": "BioMed Central", "publication": "BMC Neuroscience", "publication_date": "2006-02-07", "volume": "7", "pages": "Art. No. 11" }, { "id": "authors:b0mw2-cwe70", "collection": "authors", "collection_id": "b0mw2-cwe70", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200427-144703784", "type": "article", "title": "Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive \u03b14* Nicotinic Receptors", "author": [ { "family_name": "Fonck", "given_name": "Carlos", "clpid": "Fonck-Carlos" }, { "family_name": "Cohen", "given_name": "Bruce N.", "clpid": "Cohen-Bruce-N" }, { "family_name": "Nashmi", "given_name": "Raad", "clpid": "Nashmi-Raad" }, { "family_name": "Whiteaker", "given_name": "Paul", "clpid": "Whiteaker-Paul" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Rodrigues-Pinguet", "given_name": "Nivalda", "clpid": "Rodrigues-Pinguet-Nivalda-O" }, { "family_name": "Deshpande", "given_name": "Purnima", "clpid": "Deshpande-Purnima" }, { "family_name": "McKinney", "given_name": "Sheri", "clpid": "McKinney-Sheri" }, { "family_name": "Kwoh", "given_name": "Steven", "clpid": "Kwoh-Steven" }, { "family_name": "Munoz", "given_name": "Jose", "clpid": "Munoz-Jose" }, { "family_name": "Labarca", "given_name": "Cesar", "clpid": "Labarca-C-G" }, { "family_name": "Collins", "given_name": "Allan C.", "clpid": "Collins-Allan-C" }, { "family_name": "Marks", "given_name": "Michael J.", "clpid": "Marks-Michael-J" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" } ], "abstract": "A leucine to alanine substitution (L9\u2032A) was introduced in the M2 region of the mouse \u03b14 neuronal nicotinic acetylcholine receptor (nAChR) subunit. Expressed in Xenopus oocytes, \u03b14(L9\u2032A)\u03b22 nAChRs were \u226530-fold more sensitive than wild type (WT) to both ACh and nicotine. We generated knock-in mice with the L9\u2032A mutation and studied their cellular responses, seizure phenotype, and sleep-wake cycle. Seizure studies on \u03b14-mutated animals are relevant to epilepsy research because all known mutations linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) occur in the M2 region of \u03b14or \u03b22 subunits. Thalamic cultures and synaptosomes from L9\u2032A mice were hypersensitive to nicotine-induced ion flux. L9\u2032A mice were \u223c15-fold more sensitive to seizures elicited by nicotine injection than their WT littermates. Seizures in L9\u2032A mice differed qualitatively from those in WT: L9\u2032A seizures started earlier, were prevented by nicotine pretreatment, lacked EEG spike-wave discharges, and consisted of fast repetitive movements. Nicotine-induced seizures in L9\u2032A mice were partial, whereas WT seizures were generalized. When L9\u2032A homozygous mice received a 10 mg/kg nicotine injection, there was temporal and phenomenological separation of mutant and WT-like seizures: an initial seizure \u223c20 s after injection was clonic and showed no EEG changes. A second seizure began 3-4 min after injection, was tonic-clonic, and had EEG spike-wave activity. No spontaneous seizures were detected in L9\u2032A mice during chronic video/EEG recordings, but their sleep-wake cycle was altered. Our findings show that hypersensitive \u03b14* nicotinic receptors in mice mediate changes in the sleep-wake cycle and nicotine-induced seizures resembling ADNFLE.", "doi": "10.1523/jneurosci.3597-05.2005", "pmcid": "PMC6725918", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2005-12-07", "series_number": "49", "volume": "25", "issue": "49", "pages": "11396-11411" }, { "id": "authors:3zb2s-2mk87", "collection": "authors", "collection_id": "3zb2s-2mk87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200320-082655455", "type": "article", "title": "Effects of Random External Background Stimulation on Network Synaptic Stability After Tetanization: A Modeling Study", "author": [ { "family_name": "Chao", "given_name": "Zenas C.", "clpid": "Chao-Zenas-C" }, { "family_name": "Bakkum", "given_name": "Douglas J.", "clpid": "Bakkum-D-J" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Potter", "given_name": "Steve M.", "clpid": "Potter-S-M" } ], "abstract": "We constructed a simulated spiking neural network model to investigate the effects of random background stimulation on the dynamics of network activity patterns and tetanus induced network plasticity. The simulated model was a \"leaky integrate-and-fire\" (LIF) neural model with spike-timing-dependent plasticity (STDP) and frequency-dependent synaptic depression. Spontaneous and evoked activity patterns were compared with those of living neuronal networks cultured on multielectrode arrays. To help visualize activity patterns and plasticity in our simulated model, we introduced new population measures called Center of Activity (CA) and Center of Weights (CW) to describe the spatio-temporal dynamics of network-wide firing activity and network-wide synaptic strength, respectively. Without random background stimulation, the network synaptic weights were unstable and often drifted after tetanization. In contrast, with random background stimulation, the network synaptic weights remained close to their values immediately after tetanization. The simulation suggests that the effects of tetanization on network synaptic weights were difficult to control because of ongoing synchronized spontaneous bursts of action potentials, or \"barrages.\" Random background stimulation helped maintain network synaptic stability after tetanization by reducing the number and thus the influence of spontaneous barrages. We used our simulated network to model the interaction between ongoing neural activity, external stimulation and plasticity, and to guide our choice of sensory-motor mappings for adaptive behavior in hybrid neural-robotic systems or \"hybrots.\"", "doi": "10.1385/ni:3:3:263", "pmcid": "PMC2584804", "issn": "1539-2791", "publisher": "Springer", "publication": "Neuroinformatics", "publication_date": "2005-09", "series_number": "3", "volume": "3", "issue": "3", "pages": "263-280" }, { "id": "authors:mpy4y-t6g31", "collection": "authors", "collection_id": "mpy4y-t6g31", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110907-093554097", "type": "article", "title": "A versatile all-channel stimulator for electrode arrays, with real-time control", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Potter", "given_name": "Steve M.", "clpid": "Potter-S-M" } ], "abstract": "Over the last few decades, technology to record through ever increasing numbers of electrodes has become available to electrophysiologists. For the study of distributed neural processing, however, the ability to stimulate through equal numbers of electrodes, and thus to attain bidirectional communication, is of paramount importance. Here, we present a stimulation system for multi-electrode arrays which interfaces with existing commercial recording hardware, and allows stimulation through any electrode in the array, with rapid switching between channels. The system is controlled through real-time Linux, making it extremely flexible: stimulation sequences can be constructed on-the-fly, and arbitrary stimulus waveforms can be used if desired. A key feature of this design is that it can be readily and inexpensively reproduced in other labs, since it interfaces to standard PC parallel ports and uses only off-the-shelf components. Moreover, adaptation for use with in vivo multi-electrode probes would be straightforward. In combination with our freely available data-acquisition software, MeaBench, this system can provide feedback stimulation in response to recorded action potentials within 15 ms.", "doi": "10.1088/1741-2560/1/1/006", "pmcid": "PMC2570177", "issn": "1741-2560", "publisher": "IOP", "publication": "Journal of Neural Engineering", "publication_date": "2004-03", "series_number": "1", "volume": "1", "issue": "1", "pages": "39-45" }, { "id": "authors:7hqm2-g3890", "collection": "authors", "collection_id": "7hqm2-g3890", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WAGal04", "type": "article", "title": "Influence of chance, history, and adaptation on digital evolution", "author": [ { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Adami", "given_name": "Christoph", "orcid": "0000-0002-2915-9504", "clpid": "Adami-C-C" } ], "abstract": "We evolved multiple clones of populations of digital organisms to study the effects of chance, history, and adaptation in evolution. We show that clones adapted to a specific environment can adapt to new environments quickly and efficiently, although their history remains a significant factor in their fitness. Adaptation is most significant (and the effects of history less so) if the old and new environments are dissimilar. For more similar environments, adaptation is slower while history is more prominent. For both similar and dissimilar transfer environments, populations quickly lose the ability to perform computations (the analogue of beneficial chemical reactions) that are no longer rewarded in the new environment. Populations that developed few computational \"genes\" in their original environment were unable to acquire them in the new environment.", "doi": "10.1162/106454604773563603", "issn": "1064-5462", "publisher": "MIT Press", "publication": "Artificial Life", "publication_date": "2004-03", "series_number": "2", "volume": "10", "issue": "2", "pages": "181-190" }, { "id": "authors:jjvm8-6ek69", "collection": "authors", "collection_id": "jjvm8-6ek69", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161129-085404424", "type": "article", "title": "The Neurally Controlled Animat: Biological Brains Acting with Simulated Bodies", "author": [ { "family_name": "DeMarse", "given_name": "Thomas B.", "clpid": "DeMarse-T-B" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Blau", "given_name": "Axel W.", "clpid": "Blau-A-W" }, { "family_name": "Potter", "given_name": "Steve M.", "clpid": "Potter-S-M" } ], "abstract": "The brain is perhaps the most advanced and robust computation system known. We are creating a method to study how information is processed and encoded in living cultured neuronal networks by interfacing them to a computer-generated animal, the Neurally-Controlled Animat, within a virtual world. Cortical neurons from rats are dissociated and cultured on a surface containing a grid of electrodes (multi-electrode arrays, or MEAs) capable of both recording and stimulating neural activity. Distributed patterns of neural activity are used to control the behavior of the Animat in a simulated environment. The computer acts as its sensory system providing electrical feedback to the network about the Animat's movement within its environment. Changes in the Animat's behavior due to interaction with its surroundings are studied in concert with the biological processes (e.g., neural plasticity) that produced those changes, to understand how information is processed and encoded within a living neural network. Thus, we have created a hybrid real-time processing engine and control system that consists of living, electronic, and simulated components. Eventually this approach may be applied to controlling robotic devices, or lead to better real-time silicon-based information processing and control algorithms that are fault tolerant and can repair themselves.", "doi": "10.1023/A:1012407611130", "pmcid": "PMC2440704", "issn": "0929-5593", "publisher": "Kluwer Academic Publishers", "publication": "Autonomous Robots", "publication_date": "2001-11", "series_number": "3", "volume": "11", "issue": "3", "pages": "305-310" } ]