Cooperative Agreements

Project Summary Gaining genetic access to specific cell types in rodents, non-human primates and other vertebrate species is critical for enabling targeted circuit manipulations to understand normal brain function and brain. The use of gene regulatory elements for targeted gene expression is transforming brain circuitry studies. In response to RFA-MH-21-180, the Center for Neural Circuit Mapping (CNCM) team led by Dr. Xiangmin Xu at the Minority Serving Institution (MSI)-designated institution, University of California, Irvine (UCI) will collaborate with Dr.

PROJECT SUMMARY To understand complex neural pathways and networks and their remarkable ability to generate human behaviors, it is critical to precisely map brain connectomics in vivo. We propose to make significant advances in such brain mapping by founding the Center for Mesoscale Connectomics (CMC). We will first map the mesoscale connections between the frontal and parietal cortices. These connections likely subserve higher-order functions such as attention, decision-making, prospection, and executive control.

Project Summary/Abstract (30 lines of text limit) The ~1 billion neurons that form the human brainstem are organized at multiple scales, ranging from their cell type-specific patterns of dendritic arborization, to local circuits embedded within large-scale projection systems spanning the brainstem, and a complex nuclear architecture.

Project Summary/Abstract The proposed project will demonstrate the feasibility of generating a complete synapse-level brain map (connectome) by developing a serial-section electron microscopy pipeline that could scale to a whole mouse brain. This work will image 10 cubic millimeters, itself an unprecedentedly large dataset that may exceed tens of petabytes. Yet the mouse brain is 50 times larger. Reaching this ambitious goal will require advances in whole-brain staining, imaging, image-processing, analysis, and dissemination tools.

Project Summary: Center for whole mouse brain connectomics using high-throughput integrated volumetric electron microscopy (HIVE) Two fundamental components of the structural basis of brain function are cell type composition and the wiring diagram between those cells. Over the past decade there has been paradigm-shifting progress in understanding cell type composition of the brain. Now it’s time to systematically uncover the brain’s wiring diagram and place it into the context of cell types. Knowledge about the complete connectomes in C.

Project Summary / Abstract Upcoming brain-wide descriptions of synaptic connectivity are poised to transform our understanding of brain circuitry in the same way single-cell genomics has revolutionized our understanding of cell type diversity. The challenge of relating whole-brain wiring diagrams to cell-type genetic properties must be overcome in order to fully realize the potential of these datasets.

Project Summary/Abstract Volume electron microscopy is the only technique to-date that provides both sufficient resolution (100 μm) for the dense reconstruction of neuronal wiring diagrams. Currently, there exist two systems that have already delivered mm3-sized synaptic resolution electron microscopy stacks: Multi-beam scanning electron microscopy(Eberle et al. 2015; Ren and Kruit 2016) (mSEM) and Gridtape-based automated transmission electron microscopy(Yin et al. 2020; Maniates-Selvin et al. 2020) (Gridtape-TEM).

Project summary: This project will develop and validate a comprehensive toolset of novel technologies for imaging axonal projections across scales, and will deploy this toolset to map a complex system of cortico- subcortical projections in the macaque and human brain. We will combine the complementary strengths of three innovative microscopy techniques.

ABSTRACT Single-cell transcriptomics has revolutionized our understanding of neuronal diversity and enabled high-throughput characterization of molecular cell types across brain areas and species.

Project Summary/Abstract: Overall The overarching goal of this U19 program is to determine how neural computations across brain regions produce two core cognitive processes, working memory and decision-making, and thus to derive fundamental principles of brain function. This renewal application proposes to pursue powerful new themes that emerged from our previous work and to broaden our scope substantially.