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Mechanisms of compartmentalized plasticity in learning and memory

学习和记忆的区隔可塑性机制

基本信息

批准号：
10522519
负责人：
Seth M Tomchik
金额：
$ 38.88万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10522519
关键词：
Acetylcholine Afferent Neurons Anatomy Association Learning Automobile Driving Axon Behavior Behavioral Brain Brain Diseases Butyrates Cell physiology Cells Cyclic AMP Data Decision Making Development Dissociation Drosophila genus Drosophila melanogaster Endoplasmic Reticulum Event Genomics Goals Image Individual Investigation Learning Mammals Mediating Memory Memory Disorders Memory impairment Modeling Molecular Molecular Biology Mushroom Bodies Mutation Nervous System Neurons Neurosciences Research Odors Olfactory Learning Output Pathway interactions Pattern Process RNA Interference Reporter Resolution Retrieval Rewards Role Route Sensory Signal Transduction Stimulus Sucrose Synapses Synaptic plasticity System Testing behavioral response experience experimental study flexibility fly in vivo imaging insight knowledge base memory encoding model organism nervous system disorder neuronal circuitry neurotransmitter release novel postsynaptic presynaptic rational design response sensor sensory stimulus synaptic function therapy design

项目摘要

Project Summary A major goal of neuroscience research is to understand how experience reweights the flow of information across brain circuits. This involves plasticity that occurs at across different regions of neurons (i.e., subcellular compartmentalization). Our preliminary data revealed compartmentalization of signaling within neurons that encode olfactory memories, and further found that learning drives spatially broad elevations of Ca2+. This suggests that multiple signals are integrated across different spatial scales during learning events to modulate compartmentalized plasticity. Here we will test how compartmentalized plasticity drives the ensembles of changes across multiple spatial scales in the nervous system that leads to coherent action selection. We will test the mechanisms of compartmentalized presynaptic plasticity down to the subcellular level, using the genetically powerful, highly tractable nervous system of Drosophila melanogaster. The Drosophila mushroom body (MB) carries olfactory information from olfactory projection neurons to downstream circuits that mediate fundamental decision-making processes. We will use this system as a testbed to dissect the mechanisms of compartmentalized plasticity at the molecular levels, examine cellular integration and synaptic plasticity, and probe how these processes modulate behavioral action selection via actions on discrete circuits that modulate behavior. Understanding how memories are encoded in the brain and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Results of the present studies will provide guideposts for future research into the molecular biology of memory formation across multiple model organisms (including mammals), as the function of key molecules, cellular mechanisms, cellular compartmentalization and synaptic function, circuit motifs, and computational primitives are both conserved across species and crucial across multiple circuits & types of memory. The project will support our long-term goal of understanding of memory down to the single-cell level, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.

项目总结