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PALO ALTO, CA, United States

Jennings J.H.,University of North Carolina at Chapel Hill | Ung R.L.,University of North Carolina at Chapel Hill | Resendez S.L.,University of North Carolina at Chapel Hill | Stamatakis A.M.,University of North Carolina at Chapel Hill | And 10 more authors.

Optimally orchestrating complex behavioral states, such as the pursuit and consumption of food, is critical for an organism's survival. The lateral hypothalamus (LH) is a neuroanatomical region essential for appetitive and consummatory behaviors, but whether individual neurons within the LH differentially contribute to these interconnected processes is unknown. Here, we show that selective optogenetic stimulation of a molecularly defined subset of LH GABAergic (Vgat-expressing) neurons enhances both appetitive and consummatory behaviors, whereas genetic ablation of these neurons reduced these phenotypes. Furthermore, this targeted LH subpopulation is distinct from cells containing the feeding-related neuropeptides, melanin-concentrating hormone (MCH), and orexin (Orx). Employing in vivo calcium imaging in freely behaving mice to record activity dynamics from hundreds of cells, we identified individual LH GABAergic neurons that preferentially encode aspects of either appetitive or consummatory behaviors, but rarely both. These tightly regulated, yet highly intertwined, behavioral processes are thus dissociable at the cellular level. © 2015 Elsevier Inc. Source

Berrios J.,University of North Carolina at Chapel Hill | Stamatakis A.M.,University of North Carolina at Chapel Hill | Stamatakis A.M.,Inscopix, Inc. | Kantak P.A.,University of North Carolina at Chapel Hill | And 6 more authors.
Nature Communications

Motivated reward-seeking behaviours are governed by dopaminergic ventral tegmental area projections to the nucleus accumbens. In addition to dopamine, these mesoaccumbal terminals co-release other neurotransmitters including glutamate and GABA, whose roles in regulating motivated behaviours are currently being investigated. Here we demonstrate that loss of the E3-ubiquitin ligase, UBE3A, from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non-canonical GABA co-release and enhances reward-seeking behaviour measured by optical self-stimulation. © 2016, Nature Publishing Group. All rights reserved. Source

Inscopix, Inc. | Date: 2013-02-07

System and methods are provided for distributed microscopy. A plurality of microscopes may capture images and send them to a media server. The microscopes and the media server may be part of a local area network. The microscopes may each have a distinct network address. The media server may communicate with an operations console, which may be used to view images captured by the microscopes. The operations console may also accept user input which may be used to selectively control the microscopes.

Inscopix, Inc. | Date: 2013-02-14

Systems and methods are provided for imaging a sample. A portable slide reader may be provided that may be configured to accept a slide and that may contain one or more miniature microscopes therein. The slide reader may include a display showing images captured by the microscopes. The slide may be movable relative to the microscopes and the position of the captured image may be controllable. In some instances, images captured may be useful for DNA sequencing. Multiple color ranges may be captured for a target region, corresponding to different nucleobases.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 689.77K | Year: 2012

DESCRIPTION (provided by applicant): There is a rising emphasis today on the role of neural circuitry in neuropsychiatric disease. However we still lack crucial knowledge of both normal patterns of neural activity and how these patterns go awry in disease.Although brain researchers have already created mouse models of many human brain diseases, presently there is no technology that can visualize the activity of large numbers of individual, neurons of genetically identified types in the brains of behaving mice - ideally in multiple mice in parallel. The capacity to obtain such large-scale data sets is important towards identifying neurophysiologic signatures of brain disease and is a prerequisite for developing therapeutic means of re-tuning aberrant activity patterns. Fluorescence microscopy has key advantages for tracking neural activity. However, while conventional fluorescence microscopes offer the spatiotemporal resolution needed for imaging the brain's cellular dynamics, they neither permit studies infreely behaving mice nor are scalable for studies of large numbers of animal subjects. If fluorescence microscopes could be made small, portable, and cheap, then in principle large numbers of behaving mice could be studied in parallel. Inscopix, Inc. hasspun-out of Stanford University to commercialize miniature, integrated fluorescence microscopes - imaging technology that helps neuroscientists visualize neural circuit dynamics in awake behaving mice and rats. Prototype microscopes at Stanford are already enabling imaging of cerebellar microcirculation and permitting visualization of Ca2+ dynamics within hundreds of individual neurons (over weeks in some experiments) as the animal behaves freely in a naturalistic manner. The core miniature, integrated microscope technological innovation and its promise for studying the brain and its diseases was recently featured in Nature, MIT Technology Review, and several media outlets. In Phase I Inscopix aims to develop and test a new set of prototype microscopes that are significantly higher-performing, robust and part of a user-friendly end-to-end solution for in vivo brain imaging in freely behaving rodents. Specifically, we will: (1) Desig and create a new version of our miniaturized, integrated microscope. We will further develop the core technology and incorporate several improvements to significantly enhance imaging performance and extend the capabilities for in vivo brain imaging, including: (a) Attaining spatial resolution finer than 1 m over fields-of-viewup to 1 mm2; (b) Developing a digital, high-speed rotary commutator enabling unsupervised, imaging studies of brain activity; (c) Creating a robust and reliable microscope housing suitable for low-cost manufacturing in large volumes. (2) Develop accompanying hardware and software for data acquisition and processing. We will create a compact and user-friendly USB-compatible box for image acquisition and microscope control along with an easy-to-use Graphical User Interface (GUI). (3) Fabricate and test 10 newminiature microscopes with accompanying peripherals. We will fabricate and internally test our new designs before distributing 10 prototypes to carefully chosen beta labs for in vivo testing and validation. By the end of Phase I we expect to have receivedconsiderable in vivo usage feedback from beta labs, laying the foundation for volume production and roll-out of a market-ready product in Phase II. PUBLIC HEALTH RELEVANCE: Modern understanding of brain disease is currently undergoing a sea change, gradually shifting away from theories that emphasize a dearth or excess of neurotransmitter, and towards more sophisticated theories in which neurons of specific types exhibit improper patterns of ensemble activity underlying aberrant human behavior. This shift is especially important for disorders such as autism, which defy simple neurochemical explanations and appear to arise from circuit-level abnormalities; for disorders for which there has been much evidence to support roles for altered neurochemistry, such as schizophrenia or depression, there is rising appreciation for the equally important roles of pathologic neural circuit dynamics in causing disease phenotypes. Inscopix will develop and commercialize an innovative imaging technology for visualizing neural activity in behaving mice - and in principle, across large numbers of subjects in parallel - helping researchers obtain some of the missing knowledge about normal and aberrant neural activity patterns in mouse models of human brain disease, a key step towards developing novel therapeutics and corrective strategies.

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