Stress-induced alterations in amygdala-LC interactions

压力引起的杏仁核-LC 相互作用的改变

• 批准号: 6919221
• 负责人: ANTHONY A GRACE
• 金额: $ 32.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6919221
• 关键词: amygdala; behavior test; cold temperature; corticotropin releasing factor; drug abuse; electrophysiology; excitatory aminoacid; histology; laboratory rat; locus coeruleus; mental disorders; neuropsychology; norepinephrine; relapse /recurrence; startle reaction; stress

DESCRIPTION (provided by applicant): Stress is known to be a factor in the etiology or exacerbation of psychiatric disorders, and plays an important role in reinstatement of drug-taking behavior. This proposal will use primarily electrophysiological recordings in anesthetized rats to examine the effects of acute and chronic stress on the regulation of the locus coeruleus (LC) by the amygdalar complex. Norepinephrine and corticotropin releasing hormone have been identified as central factors in the response to stress. In particular, the noradrenergic neurons of the LC are known to have a major role in central mediation of stress responses. These neurons are driven by a number of afferent influences. One set of afferents that appears to have a primary role in stress as it relates to psychiatric disorders and relapse to drug abuse are the projections that involve the amygdala. We propose to examine amygdalar regulation of LC neuron activity, and how this system is modified by acute and chronic stress. Our central hypothesis is that chronic stress causes a sensitization of LC neuron responsivity via its effects on amygdalofugal pathways. This will be done along four specific aims: 1) to examine the physiology of projection systems connecting the basolateral amygdala complex with the LC, 2) to examine the response of this system to acute stressors (footshock), and how these responses are modified following chronic cold exposure, 3) to evaluate the nature of the change in LC neuron responsivity following chronic stress, and 4) to determine whether the alteration in LC responsivity following chronic stress can be altered by selective interruption of these amygdalar efferents. We will use primarily in vivo single unit and intracellular recording methods to examine systems-level interactions, with in vitro recordings used to measure persistent changes in LC neuronal activity and to address specific pathway-related questions as they arise. We will independently verify the behavioral effects of chronic cold exposure by measuring acoustic startle, a response that is sensitive to manipulations of the central amygdala and forebrain NE systems. We hope that a better understanding of amygdalar-coerulear systems will lead to insights into how stress-induced pathophysiology in these pathways can, in part, mediate some of the behavioral symptoms of psychiatric disease and drug-abuse disorders.

描述（由申请人提供）：已知压力是对精神疾病的病因或加剧的一个因素，并且在恢复吸毒行为中起着重要作用。该建议将主要在麻醉大鼠中使用电生理记录，以检查杏仁核复合体对急性应激对层层基因座（LC）调节的影响。去甲肾上腺素和皮质激素释放激素已被确定为应激反应的核心因素。特别是，已知LC的去肾上腺素能神经元在压力反应的中央调解中具有重要作用。这些神经元受许多传入影响驱动。与精神疾病有关的一组传入似乎在压力中起着主要作用，并且与药物滥用有关，这是涉及杏仁核的预测。我们建议检查LC神经元活性的杏仁核调节，以及该系统如何通过急性和慢性应激来修饰。我们的中心假设是，慢性应激通过其对杏仁核途径的影响引起LC神经元反应的敏感性。这将按照四个具体目的进行：1）检查将基底外侧杏仁核与LC连接起来的投影系统的生理学，2）检查该系统对急性应激源的反应（脚垫），以及这些反应在慢性冷暴露后如何修改这些响应，以跟随慢性压力后，以评估LC神经元反应的变化，并确定慢性响应的变化，并确定4）是否确定了对慢性压力的变化，并且4）是否确定了慢性压力的变化。通过选择性中断这些杏仁核的侵蚀来改变。我们将主要使用体内单个单元和细胞内记录方法来检查系统级相互作用，并用于测量LC神经元活动的持续变化并解决与特定途径相关的问题的持续变化。我们将通过测量声音惊吓来独立验证慢性冷暴露的行为影响，这种反应对中央杏仁核和前脑NE系统的操纵敏感。我们希望更好地了解杏仁核 - 毛状系统将导致对压力诱导的这些途径中的病理生理学的见解，在某种程度上可以介导精神病和药物滥用疾病的某些行为症状。