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Functional and Molecular Investigation of Physiological Astrocyte Heterogeneity

生理星形胶质细胞异质性的功能和分子研究

基本信息

批准号：
9351285
负责人：
Hua Chai
金额：
$ 4.79万
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：
2015
资助国家：
美国
起止时间：
2015-09-08 至 2019-09-07
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9351285
关键词：
Address Adult Astrocytes Brain Brain Diseases Brain region Calcium Signaling Cells Corpus striatum structure Coupled Data Distal Electrophysiology (science)Epilepsy Evaluation Excision Fluorescence-Activated Cell Sorting Follow-Up Studies Functional disorder Gene Expression Glial Fibrillary Acidic Protein Glues Heterogeneity Hippocampus (Brain)Huntington Disease Image Individual Investigation Laboratories Mass Spectrum Analysis Membrane Proteins Mental disorders Methods Molecular Monitor Mood Disorders Morphology Mus Names Neuraxis Neuroglia Neurons Physiological Physiology Process Property Proteins Proteome Proteomics Reporter Reporter Genes Role Signal Transduction Signaling Molecule Specificity Structure Synaptic Transmission Testing Therapeutic Western Blotting base biocytin brain circuitry calcium indicator experimental study insight lucifer yellow mouse model nervous system disorder neuronal circuitry neuropsychiatric disorder novel patch clamp public health relevance reconstruction synaptogenesis

项目摘要

DESCRIPTION (provided by applicant): The focus of this application is to systematically explore functional and molecular differences in astrocytes from hippocampal and striatal circuits, and thus obtain a quantitative understanding of astrocyte heterogeneity between these regions. Astrocytes are ubiquitous glial cells that interact with neurons via fine specialised distal extensions called processes. These cells serve a variety of important homeostatic roles within circuits, regulate synapse formation/removal and modulate synaptic transmission. It has generally been assumed that astrocytes are a homogenous "glue" throughout the brain. A significant bottleneck to critically assessing this view has been the lack of data on astrocyte properties in different parts of the brain. Thus we lack information that is necessary to systematically evaluate if astrocytes are functionally diverse within circuits that serve separate functions. The current application seeks to test the hypothesis that astrocytes are diverse in two brain circuitries with distinct functional roles. Specifically, this application seeks to extend insights made in our laboratory that revealed functional differences between striatal and hippocampal astrocytes, and preferential dysfunction of striatal astrocytes in mouse models of Huntington's disease. I will test the hypothesis that astrocytes in the hippocampus and striatum have distinct functional, morphological and molecular properties. This hypothesis gains support from preliminary data shown in the application that I gathered using immunohistochemical analyses of GFAP and Aldh1L1 reporter gene expression in the hippocampus and striatum. Further support comes from ongoing physiological experiments suggesting functional and morphological differences between astrocytes in these two brain regions. I will logically extend these initial findings with three specific aims. The first aim will test the hypothesis that functinal properties of striatal and hippocampal astrocytes differ. The second aim will test the hypothesis that striatal and hippocampal astrocyte morphology and astrocyte network topography differ. The third aim will test the hypothesis that the proteome of hippocampal and striatal astrocytes differ and that this can explain functional differences studied in aims 1 and 2.