The Role of the Central Amygdala and BST in Stress

中央杏仁核和 BST 在压力中的作用

• 批准号: 6999851
• 负责人: HEIDI E DAY
• 金额: $ 28.39万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999851
• 关键词: amygdala; behavioral /social science research tag; corticotropin releasing factor; enkephalins; gamma aminobutyrate; gene expression; glutamate decarboxylase; immunocytochemistry; in situ hybridization; laboratory rat; microdialysis; neuroregulation; physiologic stressor; psychological stressor; radioimmunoassay; regulatory gene; stimulus /response; substance P; thalamus

DESCRIPTION (provided by applicant): A wealth of evidence has suggested that psychological stress can precipitate or exacerbate many medical conditions, including psychiatric illnesses. One brain system that is thought to be very important for responses to stress, fear and anxiety is the central extended amygdala. This proposal is based on the assumption that knowledge of how a major output nucleus of the amygdala (the central nucleus, CEA) and a related brain region, the bed nucleus of the stria terminalis (BST) normally responds to psychological stress will ultimately help us to understand the etiology of some disorders influenced by stress. Because of the demonstrated role in fear and anxiety behaviors, a significant effort has previously been directed at demonstrating activation of the CEA. However, it has recently been shown that exposure to the psychological stress of novelty, loud noise or restraint results in a decrease (~50 percent) in amphetamine-induced c-fos mRNA expression in enkaphalin-containing neurons of the oval nucleus of the BST (BSTov) and lateral division of the CEA (CEAI), suggesting that psychological stress in fact inhibits these brain regions. Potentially, inhibition of these neurons, that are also GABAergic, would result in disinhibition of their efferent targets. These targets include the fusiform nucleus of the BST, the lateral parabrachial nucleus, and the medial CEA that collectively regulate several autonomic, endocrine, and behavioral responses that are altered by stress and anxiety. The experiments described in this application are designed to further characterize the effects of psychological stress on the BSTov and CEA. In Aim 1, potential changes in gene expression (immediate early genes, enkephalin, CRH, substance P or glutamic acid decarboxylase 65 and 67) that occur in the BSTov and CEA as a direct result of exposure to psychological stress will be assessed by semi-quantitative in situ hybridization. These changes could be used as an alternative independent measure in subsequent experiments. In addition, it will be determined if stress inhibition of the BSTov and CEAI generalizes to conditioned versus unconditioned stress and to corticotropin releasing hormone- (CRH) versus enkephalin-containing cells in these regions. Experiments in Aim 2 are designed to assess the neural circuitry involved in psychological stress effects on the BSTov and CEA. A combination of retrograde and anterograde tracing, dual immunohistochemistry, neurochemical lesions and glutamate injections will be used to determine if there is at least one brain region that projects to both the CEAI and the BSTov, that is activated by stress, and that is necessary and sufficient for the stress-induced gene expression changes in these brain regions. The potential role of GABA (y-amino butyric acid) in these stress-induced changes will also be assessed by determination of GABAergic inputs to the BSTov and CEAI, in vivo microdialysis for GABA during stress, and intracranial injection of GABAA and GABAC receptor antagonists into the BSTov and CEA prior to stress exposure. Ultimately, it is hoped that knowledge of the basic neural circuitry normally engaged following exposure to stress might help to identify some of the neural processes involved in the etiology of some psychiatric disorders.

描述（由申请人提供）：大量证据表明，心理压力会导致或加剧许多医疗状况，包括精神病。一个被认为对于应对压力，恐惧和焦虑的反应非常重要的大脑系统是中央延伸的杏仁核。该提议基于以下假设：杏仁核（中央核，CEA）和相关的大脑区域的主要输出核如何，基质末端（BST）的床核通常会对心理压力做出反应，最终会帮助我们了解某些疾病的病因学对某些疾病的病因。由于在恐惧和焦虑行为中表现出了表现的作用，因此以前已经致力于证明CEA的激活。然而，最近已经证明，在苯丙胺诱导的C-FOS mRNA表达中，新颖性，大声噪音或约束的心理压力导致BST（BSTOV）（BSTOV）（BSTOV）椭圆形神经元中的C-FOS mRNA表达降低（BSTOV）（BSTOV）和CEA（CEAI）的横向分裂（CEAI），这表明了这些精神上的压力。可能，对这些神经元的抑制作用也可能导致对其传出靶标的抑制作用。这些靶标包括BST的梭形核，外侧甲状管核和内侧CEA，这些核心集体调节了多种自主神经，内分泌和行为反应，这些反应会因压力和焦虑而改变。本应用中描述的实验旨在进一步表征心理压力对BSTOV和CEA的影响。在AIM 1中，基因表达的潜在变化（立即发生的早期基因，Enkephalin，CRH，物质P或BSTOV中发生的CEA中发生的直接导致心理压力的直接结果，将通过半量化的原位杂交评估。这些变化可以用作随后的实验中的替代独立度量。此外，还将确定对BSTOV和CEAI的应力抑制是否概括为条件与无条件的应激，以及在这些地区的激素 - CRH（CRH）与含Enkephalin的细胞的皮质激素释放。 AIM 2中的实验旨在评估对BSTOV和CEA的心理压力影响涉及的神经回路。将使用逆行和同类追踪，双重免疫组织化学，神经化学病变和谷氨酸注射的结合，用于确定是否至少有一个大脑区域向CEAI和BSTOV投射出来，这是由压力激活的，这是由压力激活的，并且足以使这些脑部的大脑表达在这些大脑中所必需，并且足以使这些大脑中的大脑表达变化。 GABA（Y-氨基丁酸）在这些应激诱导的变化中的潜在作用也将通过确定GABA能输入到BSTOV和CEAI，在压力下进行GABA的体内微透析，以及在GABAA和GABAA内注入BSTOV和CABAC受体动力学和CASEAN的颅内注入。最终，希望在承受压力后通常参与的基本神经回路的知识可能有助于确定某些精神疾病病因涉及的一些神经过程。