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：
10400074
负责人：
Alfonso Araque
金额：
$ 44.71万
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/10400074
关键词：
Address Amygdaloid structure Animal Behavior Anxiety Anxiety Disorders Astrocytes Behavior Behavioral Brain Brain Diseases CNR1 gene Calcium Communication Coupled Cues Disease Electrophysiology (science)Emotional Endocannabinoids Extinction (Psychology)Fiber Fright Genetic Goals Image Impairment Investigation Knowledge Lead Learning Light Measurement Measures Medial Methods Monitor Mus Neurons Optics Output Pathway interactions Pattern Pharmacology 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 classical conditioning 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 neurotransmitter release novel optogenetics post-traumatic stress 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.

项目摘要/摘要这项研究的总体目的是更好地了解星形胶质细胞如何中央杏仁核（CEM）调节条件恐惧行为。我们最近发现使用大脑切片 CEM中星形胶质细胞的外源激活有力调节突触传播并减少 CEM神经元活性。但是，在识别CEM星形胶质细胞在体内的作用方面仍然存在关键差距，他们在恐惧行为行为和伴侣的神经化学途径中的贡献 CEM中神经元和星形胶质细胞网络的一致活动。因此，该提议的目的是通过对星形胶质细胞和神经元活动进行测量来解决知识中的这些差距杏仁核自由地，使用光学和遗传学方法表现出小鼠。在AIM1中，我们将记录在获得，表达和灭绝的恐惧期间，星形胶质细胞在CEM中的活性条件行为。他们将提供第一个生理证据，表明星形胶质细胞是专门的并在条件恐惧反应的特定阶段进行差异激活。在目标2中，我们将确定CEM星形胶质细胞在调节杏仁核驱动的反应中是否具有内源性作用。它还将进一步测试星形胶质细胞内源性大麻素信号在这些行为中的作用。在目标3中我们将确定CEM星形胶质细胞外源激活的细胞和行为后果使用化学发生和光遗传学方法。总而言之，拟议的研究将提供很多关于星形胶质细胞在中央杏仁核中的作用的更详细的图片，并扩展了我们最近的前体体杏仁核切片研究。这些知识将为治疗新的药理学策略铺平道路通过利用星形胶质细胞受体表达的罕见特征，焦虑/恐惧障碍调节他们的活动。因此，我们的研究将有助于产生一种新的策略来治疗神经系统疾病，例如焦虑，创伤后压力综合征，通过靶向相对研究杏仁核中的细胞类型。