Circuit Diagrams

Project Summary The ultimate product of our Center will be a series of comprehensive developing human and non-human primate (NHP) brain atlases of unprecedented cellular, spatial, and anatomical resolution. In Aim 1, we will characterize transient cell populations, establish the diversity of cell types present in specific brain regions, unravel complex developmental trajectories, and reveal conserved and divergent cell-type specific features. We will jointly profile of single nucleus RNA (snRNA-seq) and accessible chromatin (snATAC-seq) using the 10X Genomics snMultiome platform.

Abstract Understanding cell identities and their spatial distributions throughout different regions of the human brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of the cell-types present in the human brain have been defined molecularly, the different subtypes within these categories along with their locations are far from understood. Gene expression drives cell programs and states that underlie distinct brain functions.

PROJECT SUMMARY The adult human brain is comprised of numerous cell types exhibiting specific transcriptomic and epigenomic signatures associated with their spatial location, connectivity, and function. Although systematic efforts are underway to characterize cell types in the adult human brain, the transitional cell types and cell states in developing human brains are not fully defined.

Project Summary/Abstract The overarching objective of this proposal is to develop a robust approach to map the brain's connections quickly, accurately, and cost-effectively. Past efforts to address the challenge of teasing apart the complex connectome of the mammalian brain were subject to a steep trade-off between throughput/efficiency and resolution. Two cutting-edge neuronal mapping techniques—barcoding based connection mapping (BARseq) and expansion microscopy (ExM)—have proven they can achieve efficient and high-resolution connection mapping within mammalian neural tissue.

Abstract Neural circuits composed of interconnected neurons with distinct properties lay the physical foundation of any brain function. Identifying connections between individual neurons is central to understand how information is processed and propagated in the brain. While emerging high throughput light microscopy technologies are highly promising in allowing whole brain scale imaging at the single cell level, optical resolution limitation prevents their use in differentiating densely labeled neuronal processes in the same brain.

The complex behaviors of all vertebrates are determined by the brain where neurons are connected by synapses. The average volume of synapses corresponds to a sphere of ~400 nm radius—a size scale that can barely be resolved using conventional optical microscopy methods. Synapses are tightly packed with molecular assemblies of synaptic vesicles, synaptic and cytoskeletal proteins and neurotransmitter receptors.

At the end of 2020, the IARPA MICrONS program will conclude with an automated reconstruction of all neurons in a cubic millimeter of mouse visual cortex, along with the neurons’ synaptic connectivity and calcium-imaged responses to video stimuli. We believe that this dataset could become the most widely used resource in the field of cortical circuits, but more work is required to realize this potential.

Summary Demand for the common marmoset (Callithrix jacchus) in biomedical research has increased tremendously over the past five years, as they have emerged as a critical biomedical model system in a variety of study disciplines. The increased use of marmosets has been most acute in neuroscience, where the need to study cognition, behavior, and mental illness in primate models has grown.

Project Summary The common marmoset (Callithrix jacchus) has experienced unprecedented growth in research across the United States and is rapidly emerging as a likely keystone biomedical model system in the next chapter of scientific discovery.

PROJECT SUMMARY/ABSTRACT The common marmoset (Callithrix jacchus) has emerged as a critically important and tractable non-human primate (NHP) model for neuroscience research accommodating genetic manipulation and directed breeding. Several barriers to the adoption of marmoset models by the neuroscience community exist, including a small census size in the United States (fewer than 2,500 animals), poor communication about resource availability, a poor understanding of the strengths and limitations of marmosets in research, and a lack of a formal structure for coordinating the sharing of info