Theory & Data Analysis Tools

Defining motor neuron diversity from embryo to adulthood and generating tools for in vivo and in vitro access

PROJECT SUMMARY/ABSTRACT In order to understand neurological diseases, it is essential to identify the affected neuronal cell types, create model systems that accurately recapitulate normal function and disease phenotypes, and develop tools that allow cellular manipulations. Motor neurons in the spinal cord control body movement by communicating central motor commands with muscle targets.

Mechanisms of Transplanted Cortical Interneuron Survival and Function

Project Summary Cortical interneurons (cINs) are inhibitory cells that are born in surplus far from the cortex. During prenatal timepoints, cIN precursors migrate into the mouse visual cortex (V1) where only a fraction are selected to survive. Once integrated into the V1 circuit, cINs expressing parvalbumin (PV) or somatostatin (SST) trigger a temporally restricted period of plasticity that is required for normal visual experience. The underlying molecular factors and the role cellular activity plays in the selection of cIN survival and cIN-mediated plasticity are not fully understood.

Hormonal regulation of sensory processing during parental care

PROJECT SUMMARY/ABSTRACT Does the way we hear sounds change when we become parents? This proposal will causally test if hormones involved in parental behavior affect the neural circuitry underlying offspring auditory cue processing in parents. It has long been known that offspring sensory cues, such as baby cries, elicit the necessary and appropriate behavioral responses from parents. How these sounds are encoded by the brain to elicit behavioral responses is not well understood.

Gene regulatory networks influencing neuron-microglia interactions in fetal brain development.

Project Summary/Abstract The prenatal period is a sensitive and critical time for brain development characterized by waves of neurogenesis, neuronal migration, and formation of neural networks. In the first and second trimester, microglia are the dominant immune cells of the brain and participate in a variety of processes essential to brain development, including secreting neurotropic factors and engulfing apoptotic neural progenitor cells. Fetal microglia dysfunction can lead to aberrant cortical lamination, resulting in an increased risk of brain pathology.

A Shared Neuroscience Platform for National Dissemination and Training in Brain Organogenesis, Behavioral and Brain Disease Models, Viral Vectors, and Imaging Technologies

Advances in neuroscience depend on robust in vivo and in vitro models with innovative technologies to carry out functional and mechanistic studies accompanied by advanced imaging techniques. The Human Brain Organogenesis Program (HBOP), Behavioral and Functional Neuroscience Laboratory (BFNL), Gene Vector and Virus Core (GVVC), and Neuroscience Microscopy Services (NMS) make up a platform, the Stanford Neuroscience Research Center (SNRC), for centralization and dissemination of innovative neuroscience models, reagents and methods.

Dissemination of FlyWire, A Whole-Brain Connectomics Resource

This proposal will disseminate FlyWire, a Drosophila whole brain connectomics resource. We used advances in AI to segment all neurons from a whole brain EM volume called FAFB. The automated segmentation is of high enough quality that, in combination with innovative proofreading tools, scientists can relatively quickly proofread circuits of interest. The community of current collaborators includes about 160 scientists from 40 labs, who have so far succeeded at proofreading more than 15% of the neurons in the fly brain. Several publications have resulted, and more are on the way.

Dissemination of MAPseq and BARseq for high-throughput brain mapping

The goal of this project is to disseminate MAPseq and BARseq to the broader neuroscience community. These are novel methods developed in my laboratory based on high-throughput DNA sequencing for determining neuronal circuitry. Neurons transmit information to distant brain regions via long-range axonal projections. In some cases, functionally distinct populations of neurons are intermingled within a small region.

Virtual observatory of the cortex: organelles, cells, circuits, and dynamics

We propose to create VOrtex, a Virtual Observatory for the Cortex: Spanning the Scales of Organelles, Cells, Circuits, and Dynamics. The observatory will disseminate an existing dataset: an automated reconstruction of all cells in a cubic millimeter of mouse visual cortex, along with the synaptic connectivity of the neurons and calcium-imaged responses to video stimuli. The cubic millimeter volume spans all layers of cortex and four visual areas (V1, LM, AL, RL). A team of human proofreaders will detect and correct the remaining errors in the automated segmentation.

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