Project Summary/Abstract To learn novel actions through reinforcement, a fundamental mechanism of motor learning, the brain needs to causally link previously performed movements to their resulting outcomes.
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.
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.
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.
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.
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.
PROJECT SUMMARY / ABSTRACT To survive, animals must learn appropriate associations between sensory cues and motor actions through a process of trial and error. We expect that this learning will strengthen the synaptic connections between neurons representing the sensory cue and neurons initiating the motor action.
Project Summary/Abstract This proposal aims to delineate the electrical and molecular diversity of the suprachiasmatic nucleus (SCN) and provide new evidence for receptor-expressing subtypes of SCN neurons using novel nanowire arrays that allow single cell recording at 1024 contacts simultaneously. The SCN is among the most robust and far-reaching networks of the brain.
Project Summary Learning is a fundamental function of the brain: sensory representations must be flexible to adjust to changes in environmental demands and experience, thus allowing us to adapt to the world around us. Understanding the mechanisms of learning are important not only for normal function of the brain but also in disease, for example, after unilateral hearing loss. One important but often overlooked principle of learning is the importance of feedback from other brain areas.
Project Summary/Abstract Candidate Goals and Mission Relevance: The applicant’s broad, long-term objective is to investigate how high- (circuit/behavioral) and low- (subcellular/molecular) level organizational principles of the brain cooperate to drive learning.
