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Dynamic Striatal Astrocyte-Neuron Interactions: An Integrated Experimental and Computational Study

动态纹状体星形胶质细胞-神经元相互作用：综合实验和计算研究

基本信息

批准号：
10393076
负责人：
Marsa Taheri
金额：
$ 0.25万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10393076
关键词：
Adult Affect Alzheimer&apos s Disease Astrocytes Attenuated BRAIN initiative Behavior Behavioral Biochemical Biological Brain Brain Diseases Brain region Buffers Cells Communication Computer Models Computing Methodologies Corpus striatum structure Coupled Data Data Analyses Electrophysiology (science)Epilepsy Experimental Models Extracellular Space G-Protein-Coupled Receptors Genetic Goals Huntington Disease Hyperactivity Image In Situ Ions Knock-in Mathematics Measurable Measurement Measures Mediating Methods Modeling Modification Mus Na(+)-K(+)-Exchanging ATPase Neuroglia Neurons Obsessive compulsive behavior Obsessive-Compulsive Disorder Outcome Pathway interactions Physiological Pump Receptor Activation Regulation Reporting Rodent Role Serine Signal Transduction Silicon Site Slice Stroke Study models Synapses Testing Time Work attenuation base behavioral outcome brain cell brain circuitry computer framework computer studies experimental study extracellular in vivo innovation insight large scale data mathematical model millisecond nervous system disorder neural circuit neuronal excitability novel novel strategies optogenetics patch clamp predictive modeling response time use tool

项目摘要

Project Summary/Abstract Astrocytes comprise up to half of mammalian brain cells. Accumulating evidence from multiple brain circuits suggests that astrocytes, through their intracellular Ca2+ signaling, regulate and modulate neuronal activity on single-cell and network-wide levels and on a broad range of timescales—from milliseconds to days and weeks. Altered astrocyte Ca2+ signaling has also been implicated in a variety of brain disorders, including Huntington’s Disease, Alzheimer’s Disease, obsessive-compulsive disorder, stroke, and epilepsy. However, much remains to be done to uncover how astrocytes contribute to brain function. First, there is a shortage of experimentally based, sophisticated computational approaches for astrocyte data analysis and interpretation that could aid in guiding new, hypothesis-driven and rigorous experiments. Second, there is a dearth of data where astrocyte-neuron interactions have been explored carefully in a single model brain circuitry with behavioral readouts. I seek to make inroads in both of these topics by exploring astrocyte-neuron interactions in the striatum using experimental and computational approaches. This study proposes to elucidate the physiological interplay between astrocytes and neurons in striatal neural circuits. In Aim 1, experimental and computational approaches will be integrated to study in situ striatal astrocyte Ca2+ signaling and its effect on neuronal excitability on timescales of seconds. For this aim, astrocyte Ca2+ activity will be perturbed in situ using genetic knock-in and chemogenetic approaches. In Aim 2, an optogenetic tool will be developed and used to transiently stimulate striatal astrocyte Ca2+ responses in situ and in vivo, and investigate its effects on neuronal activity and behavior. The results from these will provide much needed insight into astrocyte-neuron communication in a well-characterized brain circuit relevant to behavior and neurological diseases. In addition, these studies will result in two sets of tools for future research: a novel optogenetic tool for astrocyte manipulation and an experimentally-verified mathematical model of astrocyte- neuron interactions.

项目总结/文摘