Research Projects

7. PROJECT SUMMARY/ABSTRACT Mental health disorders cause immense personal suffering and represent a significant societal burden. Recent research emphasizes the potential of psychiatric electroceutical interventions (PEIs) – bioelectronic treatments that employ electrical stimulation to affect and modify brain function – to effectively treat such disorders. Novel PEIs, however, also raise significant ethical concerns. Not uncommonly, they are negatively associated with historically controversial interventions such as electroconvulsive therapy and lobotomy.

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.

Project Summary The goal of this proposal is to develop a widely adoptable, high-throughput, functional connectomics platform to semi-automatically reconstruct and analyze the synaptic connectivity of functionally characterized neuronal microcircuits. We will develop this pipeline in the context of understanding neural microcircuits that control walking, using the Drosophila ventral nerve cord (VNC) as a model system.

Project Summary/Abstract We have recently published a 3D electron microscopy volume of the whole fruit fly brain. However mapping of synaptic `wiring diagrams' or connectomes of neuronal circuits from this volume is currently completely manual and therefore slow. Our long-term goal is to increase understanding of how circuits process and transform information, both by accelerating connectomics mapping, and increasing the power and accessibility of analysis tools.