Vanessa Tolosa, Ph.D. - US grants

? DESCRIPTION (provided by applicant): The brain is a massively interconnected network of specialized circuits. Even primary sensory areas, once thought to support relatively simple, feed-forward processing, are now known to be parts of complex feedback circuits. All brain functions depend on millisecond timescale interactions across these brain networks, but current approaches cannot measure or manipulate these interactions with sufficient resolution to resolve them. We need the capacity to measure and manipulate the activity large ensembles of neurons distributed across anatomically or functionally connected circuits. That technology does not yet exist, a lack that motivates our efforts to develop a new system for large scale, multisite recording and manipulation that takes integrates biocompatible polymer electrodes, new headstage amplifiers, a new Ethernet-based data transmission system and open source, real-time cross-platform software. This system will support recordings and manipulations across thousands of channels in awake, behaving animals as well as closed loop feedback for the next generation of experiments. Our Specific Aims are 1) To develop new high-density, double-sided polymer recording/manipulation probes, 2) To develop new high-density headstage chips, integrated electrode- headstage assemblies and surgical techniques for implanting them, and 3) To develop a low-cost, powerful data acquisition system with open-source software and real-time capabilities. We have assembled a unique team of scientists and engineers with expertise spanning polymer electrode technology, integrated electronics, real-time systems, large-scale recording, and commercial experience. Our combined expertise will allow us to create and provide to the neuroscience community an integrated system that will allow for large scale, distributed measurements and manipulation of neural activity across many sites in awake, behaving animals.

? DESCRIPTION (provided by applicant): The brain is a massively interconnected network of regions, each of which contains neural circuits that process information related to combinations of sensory, motor and internal variables. Adaptive behavior requires that these regions communicate: sensory and internal information must be evaluated and used to make a decision, which must then be transformed into a motor output. Despite the importance of this question, we know relatively little about the principles of how spiking activity in one region influences activiy in downstream areas, particularly in the context of cognitive operations like decision-making. Here we propose to address this question by focusing on how the ventral striatum (VS), a region critical for motivational control of behavior receives and processes information from two important upstream regions, the orbitofrontal cortex (OFC) and the hippocampus (HP). We have assembled a unique team of scientists with complementary expertise studying the HP (Frank), OFC and VS (Kepecs), using synergistic technologies for large-scale recordings using novel polymer electrodes (Frank/Tolosa) with improved optogenetic identification of projections (Kepecs), and a team of statistical and computational researchers providing complementary analytical expertise in dimensionality reduction (Machens), statistical modeling (Eden/Kramer) and normative models (Ganguli). Our combined expertise will allow us to (1) measure large populations of neurons across the brain regions, (2) identify and (3) manipulate the neurons connecting them in order to (4) test for the first time a range of hypotheses about different modes and circuits for information transmission across regions. Beyond revealing how the OFC, HP and VS communicate during learning and decision-making, our approach will provide new experimental tools and computational methods for systems neuroscience, as well as new insights into the general principles of information transmission across regions.

? DESCRIPTION (provided by applicant): The brain is a massively interconnected network of specialized circuits. Even primary sensory areas, once thought to support relatively simple, feed-forward processing, are now known to be parts of complex feedback circuits. All brain functions depend on millisecond timescale interactions across these brain networks, but current approaches cannot measure or manipulate these interactions with sufficient resolution to resolve them. We need the capacity to measure and manipulate the activity large ensembles of neurons distributed across anatomically or functionally connected circuits. That technology does not yet exist, a lack that motivates our efforts to develop a new system for large scale, multisite recording and manipulation that takes integrates biocompatible polymer electrodes, new headstage amplifiers, a new Ethernet-based data transmission system and open source, real-time cross-platform software. This system will support recordings and manipulations across thousands of channels in awake, behaving animals as well as closed loop feedback for the next generation of experiments. Our Specific Aims are 1) To develop new high-density, double-sided polymer recording/manipulation probes, 2) To develop new high-density headstage chips, integrated electrode- headstage assemblies and surgical techniques for implanting them, and 3) To develop a low-cost, powerful data acquisition system with open-source software and real-time capabilities. We have assembled a unique team of scientists and engineers with expertise spanning polymer electrode technology, integrated electronics, real-time systems, large-scale recording, and commercial experience. Our combined expertise will allow us to create and provide to the neuroscience community an integrated system that will allow for large scale, distributed measurements and manipulation of neural activity across many sites in awake, behaving animals.