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.
DESCRIPTION (provided by applicant): The purpose of this RFA is to promote the integration of experimental, analytic and theoretical capabilities for the examination of neural circuits and systems. This proposal is highly responsive to the RFA in that it links several different neuroscience labs to develop new technologies that provide for simultaneous multistate imaging and applies these technologies to the examination of how neuronal dynamics in mammalian cortex varies as a function of brain state and development.
DESCRIPTION (provided by applicant): The system that controls smooth pursuit eye movements is one of the most accessible, promising systems for understanding how neural circuits transform sensory inputs into actions. Pursuit is a natural, ecologically- relevant behavir that allows primates to track moving objects of interest in the visual world.
DESCRIPTION (provided by applicant): To address the core question underlying the Obama Brain Initiative to better understand the function of complex brain circuits, we propose a multi-scale recording and data analysis project to study the dynamical interactions between sensory cortex, motor cortex, and the basal ganglia in the process of motor planning and execution. The multi-scale approach will involve simultaneous recordings at the cellular, network, and systems level in head-fixed behaving mice trained to perform a rewarded locomotor task.
DESCRIPTION (provided by applicant): The anatomical substrates and cellular mechanisms underlying reward-dependent learning have been studied for decades, but the specific circuit and network interactions between the cortex, striatum, and midbrain that mediate action selection have not been systematically investigated. Here, we bring together three different investigators with specialized expertise in each of these three brain regions.
DESCRIPTION (provided by applicant): Severe to moderate traumatic brain injury (smTBI) annually afflicts many hundreds of thousands of Americans producing chronic cognitive disabilities that lack effective treatments. The present proposal will develop a critical first-in-an early clinical feasibility study to support a next generation device to provide central thalamic deep brain stimulation (CT-DBS).
Histone modification carries rich epigenetic information that constitutes a mechanism of cellular memory. Single cell analysis of histone modification in conjunction with transcriptome could help uncover this critical layer of cellular memory and lead to better definition of cell types and states in the brain. Here, we propose to develop an ultra-high throughput method, known as Paired-Tag, for joint profiling of histone modifications and transcriptome in single cells.
Project Summary The BICCN has recently completed a broad survey of the cellular components of motor cortex, including transcriptomic profiling, patch-seq, multiplexed FISH, inter-areal connectivity, and single neuron morphology. Missing from this view is a detailed picture of how individual neurons and neuronal types interconnect, in large part because acquiring a comprehensive picture of individual neuronal connections is best achieved with the difficult methods of large-scale electron microscopic reconstructions.
Project summary, Scalable technologies for brain-wide connectomics of transcriptomic cell types: focus on brainstem This proposal is to develop a scalable pipeline to combine high-resolution morphology and molecular classification of individual neurons to define morpho-molecular cell types in the brain. Complete morphology of individual neurons provides insights of connectivity and information processing in the brain and reveals how neuronal activity is routed across brain areas.
PROJECT ABSTRACT To meet the goal of the BRAIN Initiative Cell Census Network to catalogue and produce molecular profiles of every cell type in the human brain; order-of-magnitude improvements in single-cell assay throughput and coverage are required.
