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Astrocyte activity in amygdala-related fear conditioned behaviors

杏仁核相关恐惧条件行为中的星形胶质细胞活性

基本信息

批准号：
10593940
负责人：
Alfonso Araque
金额：
$ 44.72万
依托单位：
UNIVERSITY OF MINNESOTA
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：
2020-06-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10593940
关键词：
Address Amygdaloid structure Animal Behavior Anxiety Anxiety Disorders Association Learning Astrocytes Behavior Behavioral Brain Brain Diseases CNR1 gene Calcium Communication Coupled Cues Disease Electrophysiology (science)Emotional Endocannabinoids Extinction Fiber Fright Genetic Goals ITPR1 gene Image Impairment Investigation Knowledge Learning Light Measurement Measures Medial Methods Monitor Mus Neurons Neurotransmitters Optics Output Pathway interactions Pattern Phase Photometry Physiological Play Post-Traumatic Stress Disorders Preparation Property Research Role Signal Transduction Slice Specificity Synapses Synaptic Transmission Syndrome Testing Transgenic Mice Work calcium indicator cell type cellular targeting conditioned fear designer receptors exclusively activated by designer drugs endocannabinoid signaling excessive anxiety gain of function in vivo information processing insight loss of function melanopsin memory process mouse model nervous system disorder neurochemistry neurotransmission novel optogenetics pharmacologic post-traumatic stress receptor receptor expression response selective expression synaptic function synaptic inhibition targeted treatment

项目摘要

PROJECT SUMMARY/ABSTRACT The overall goal of this research is to better understand how astrocytes in the medial subnucleus of the central amygdala (CeM) modulate conditioned fear behaviors. We recently found using brain slices that exogenous activation of astrocytes in the CeM powerfully regulates synaptic transmission and decreases CeM neuronal activity. However, critical gaps remain in identifying the role of CeM astrocytes in vivo, their contribution during fear conditioned behaviors, and the neurochemical pathways that couple the concerted activity of neuronal and astrocyte networks in the CeM. The goal of this proposal is therefore to address these gaps in knowledge by performing measurements of astrocytic and neuronal activity in the amygdala in freely, behaving mice using optical and genetic methods. In Aim1 we will record the activity of astrocytes in the CeM during the acquisition, expression and extinction of cued fear conditioned behaviors. They will provide the first physiological evidence that astrocytes are specifically and differentially activated during specific phases of conditioned fear responses. In Aim 2 we will determine whether CeM astrocytes have an endogenous role in modulating amygdala-driven responses. It will also further test the role of astrocytic endocannabinoid signaling in these behaviors. In Aim 3 we will determine the cellular and behavioral consequences upon exogenous activation of CeM astrocytes using chemogenetic and optogenetic methods. In summary, the proposed studies will provide a much more detailed picture on the role of astrocytes in the central amygdala and extend our recent ex vivo amygdala slice studies. This knowledge will pave the way for new pharmacological strategies to treat anxiety/fear disorders, by taking advantage of the uncommon profile of receptor expression of astrocytes to regulate their activity. Therefore, our studies will contribute to generate a new strategy to treat neurological diseases, such as anxiety, post-traumatic stress syndrome by targeting a relatively understudied cell type in the amygdala.

项目总结/文摘