Circuit Based Analysis of Fear and Stress

基于电路的恐惧和压力分析

• 批准号: 6850594
• 负责人: JOHN A MORRISON
• 金额: $ 23.73万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6850594
• 关键词: amygdala; auditory cortex; auditory stimulus; behavioral /social science research tag; brain electrical activity; brain mapping; brain metabolism; conditioning; confocal scanning microscopy; dendrites; fear; laboratory rat; medial geniculate body; neural plasticity; neural transmission; neuroanatomy; neurochemistry; neuropsychology; prefrontal lobe /cortex; stress; synapses

This project investigates structural and molecular synaptic plasticity in the circuits mediating fear conditioning (FC), related circuits affected by stress, and the synaptic basis for fear/stress interactions. These experiments will be done in collaboration with Projects 1, 4, and the QMC. Synaptic basis of FC. The convergent projections to lateral amygdala (LA) from the medial geniculate nucleus (MGn) and auditory cortex (AC) will be labeled through anterograde transport and analyzed ultrastructurally in fear conditioned and control (unpaired stimuli) animals. Quantitative immunogold will be used to develop a molecular profile of the synapses mediating FC. We hypothesize that the molecular profile of the synapse will be altered by FC. Neuronal reconstructions will also be carried out in LA to determine the effects of FC on dendritic arbor, spine number, and morphology. We hypothesize that molecular synaptic alterations will predominate over structural alterations as mediators of FC. Synaptic alterations from stress. We hypothesize that chronic and acute behavioral stress will result in synaptic alterations in both amygdala and the medial prefrontal cortex (mPFC) and that stress-induced alterations will be manifested in both mPFC/BA circuits and the auditory circuits that mediate FC. The impact of chronic or acute stress on the molecular profile of key synapses and dendrites morphology will be assessed for both sets of circuits. Spine number will be assessed stereologically in both LA and BA, to determine the nuclear target of the stress-induced spine increase. An analysis of dendritic arborization, spine density, and spine morphology will be done on the neurons that reciprocally connect mPFC and BA, as well as neurons in LA. These studies will determine the circuits that are directly affected by stress that might impact FC. Interactions between stress and FC. Animals that have had FC and exposed to stress will be analyzed with the same ultrastructural and morphologic approaches outlined above to directly assess the interactive synaptic effects. In addition, we will determine whether inactivation of the amygdata blocks the stress-induced plasticity in mPFC, as such inactivation does block FC.

本项目研究了介导恐惧条件反射（FC）的神经回路的结构和分子突触可塑性、受应激影响的相关神经回路以及恐惧/应激相互作用的突触基础。这些实验将与项目1、项目4和QMC合作完成。FC的突触基础。在恐惧条件和对照（未配对刺激）动物中，通过顺行运输对内侧膝状核（MGn）和听觉皮层（AC）向外侧杏仁核（LA）的会聚投影进行标记和超微结构分析。定量免疫金将用于开发介导FC的突触的分子图谱。我们假设突触的分子结构会被FC改变。神经元重建也将在LA进行，以确定FC对树突乔木，脊柱数量和形态的影响。我们假设分子突触改变将主导结构改变作为FC的介质。压力引起的突触改变。我们假设慢性和急性行为应激会导致杏仁核和内侧前额叶皮层（mPFC）的突触改变，并且应激诱导的改变将在mPFC/BA回路和介导FC的听觉回路中表现出来。慢性或急性应激对关键突触和树突形态的分子特征的影响将在两组电路中进行评估。脊柱数量将在LA和BA中进行立体评估，以确定应力诱导的脊柱增加的核目标。将对mPFC和BA相互连接的神经元以及LA的神经元进行树突树突化，脊柱密度和脊柱形态学的分析。这些研究将确定哪些回路直接受到可能影响FC的压力的影响。应力与FC之间的相互作用。研究人员将使用与上述相同的超微结构和形态学方法对FC和应激动物进行分析，以直接评估相互作用的突触效应。此外，我们将确定杏仁核失活是否会阻断mPFC中应力诱导的可塑性，因为这种失活确实会阻断FC。