Circuit Diagrams

Project Summary – Abstract Neuroscientists are getting close to building realistic bioengineered ex vivo human brain models by: (1) introducing perfusable vascular networks to maintain tissue viability and promote 3D brain model growth; (2) generating the full complement of currently missing cell types; (3) building particular brain regions and exploring specific input and output signals.

Abstract More than 500,000 children in the USA and Canada suffer from epilepsy today. Unmanaged, epilepsy can result in cognitive decline, social isolation and poor quality of life, and has substantial economic impact on families and society. 30% of children with epilepsy continue to have seizures while on anti-seizure medication, a condition known as drug resistant epilepsy (DRE). Properly selected, up to 70% of DRE patients become seizure-free after surgery. Nevertheless, epilepsy surgery carries with it risks proportional to its level of invasiveness.

From Electron Microscopy to Neural Circuit Hypotheses: Bridging the gap Recent advances in experimental technology promise rapid progress in developing a mechanistic understanding of how neural circuit structure, at the synaptic scale, leads to complex sensory, cognitive, and motor behaviors. Volume EM techniques have advanced to the point that neural tissue can be imaged at synaptic resolution in volumes large enough (~ 100 µm) to contain a entire small neuron .

Project Summary We propose to build a next generation crowdsourcing platform (code named “FlyWire”) for mapping the fly connectome using transmission electron microscopy images that were acquired at Janelia Research Campus. FlyWire will depart from EyeWire, a previous crowdsourcing platform, in two major ways: (1) Much higher throughput will be attained by leveraging the latest in deep learning. (2) FlyWirers will consist mainly of fly neuroscientists, while EyeWirers were primarily nonscientists.

Project Summary Trans‐synaptic bidirectional tracing tools for imaging and omics analysis A central question in systems neuroscience is how hormones, such as estrogen, regulate animal behavior at the level of synapses and circuits. The Shah lab has recently identified hormone-responsive neuronal populations in the hypothalamus and amygdala that mediate distinct behaviors between the sexes.

ABSTRACT To interpret the detailed ultrastructural information of the connectomes in Drosophila and other species, it will be necessary to know the physiological functions of synapses between specific cell types. One key step will be the identification of the neurotransmitter receptors that reside at each site and the connectivity of post-synaptic receptors to specific presynaptic partners. This proposal will combine three cutting-edge technologies to establish methods for tagging neurotransmitter receptors and mapping their subcellular location and synaptic partners.

! PROJECT SUMMARY Deciphering the brain’s wiring diagram is widely thought to be necessary towards understanding how brain circuits process information. However, this goal is extremely challenging because currently available methods to study brain connectivity suffer from important limitations.

TOWARD 3D HUMAN BRAIN-LIKE TISSUES FOR TARGETING DYSREGULATED SYNAPSE AND PROTEOSTASIS MECHANISMS IN AUTISM SPECTRUM DISORDER Autism spectrum disorder (ASD) is a neurodevelopmental disease affecting nearly 1/50 children in US with an estimated $268 billion in annual costs. The disease is characterized by significant behavioral abnormalities that are often devastating to the quality of life for these patients. Behavior is directly related to the underlying changes of the central nervous system (CNS) brain tissue.

Project Summary/Abstract The BRAIN initiative has put forth the development of a neuronal cell-type census as the first step towards mapping the structure and components of neuronal circuits.

Project Summary When learning new skills, experience with previously-learned skills can facilitate faster learning by constraining behavioral exploration and shaping, a concept known as “structural learning”3,4. The motor cortex plays an essential role in learning new skills5,6, and its initially variable activity is shaped and consolidated over learning7–10. However, how previous experience modulates exploration and shaping of cortical network activity to facilitate new skill learning is not well understood.