NEURAL PLASTICITY UNDERLYING FEAR CONDITIONING IN MICE

小鼠恐惧条件下的神经可塑性

• 批准号: 6538355
• 负责人: Michael Rogan
• 金额: $ 4.81万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6538355
• 关键词: amygdala; behavior test; behavioral /social science research tag; calmodulin dependent protein kinase; conditioning; electrostimulus; enzyme activity; evoked potentials; fear; gene expression; genetically modified animals; laboratory mouse; long term potentiation; neural information processing; neural plasticity; protein kinase A; synaptic vesicles; thalamocortical tract; wakefulness

Understanding the processing of emotion by the brain is essential for the development of affective treatment of emotional disorders. The study of the neural substrates of emotion has been much advanced by the use of fear conditioning (FC) to study how an aversive association is formed with a neutral auditory conditioned stimulus (CS). Studies in the rat have identified the amygdala as essential for this process: CS processing in the lateral nucleus of the amygdala (LA) is modulated by FC, and also by artificial induction of neural plasticity (LTP) by tetanic electrical stimulation of CS pathways to LA. To study the synaptic plasticity underlying FC, I will develop a mouse preparation that permits independent measurement of the synaptic efficacy of the cortical and thalamic CS pathways to LA in the same awake mouse during FC, as well as concurrent measures of behavior and of CS processing. Electrical stimulation will be use to directly and independently manipulate the transmission properties of CS pathways ti assess the effect of synaptic plasticity in NL synapses on CS processing. Further, by using molecular genetic techniques to reversibly modify the molecular response of LA to plasticity-inducing stimulation (FC, LTP induction) in vivo, we will investigation the molecular mechanisms underlying these forms of plasticity. We will study the effects of a constitutively active form of CamKII, and of an inhibitor of PKA, in AL on electrophysiological correlates of FC and LTP. CaMKII and PKA are implicated in LTP and in behavioral measures of FC.

了解大脑对情绪的处理对于发展情绪障碍的情感治疗至关重要。通过使用恐惧调节（FC）来研究如何与中性的听觉条件刺激（CS）形成厌恶关联，对情绪神经基板的研究已经大大提高了。大鼠中的研究已经确定杏仁核对于此过程至关重要：杏仁核（LA）的外侧核中的CS加工是通过FC调节的，也通过人工诱导神经可塑性（LTP）来调节CS途径的CS途径。为了研究FC的基础突触可塑性，我将开发一种小鼠制剂，该制剂允许在FC期间在同一清醒小鼠中独立测量皮质和丘脑CS通向LA的突触功效，以及同时的行为和CS处理的衡量。电刺激将用于直接和独立地操纵CS途径的传输特性Ti评估突触可塑性在NL突触对CS处理中的影响。此外，通过使用分子遗传技术在体内逆转地修改LA对塑性诱导刺激（FC，LTP诱导）的分子反应，我们将研究这些形式的可塑性形式的分子机制。我们将研究CAMKII的组成型活性形式和PKA抑制剂在AL中对FC和LTP的电生理相关性的影响。 CAMKII和PKA与LTP和FC的行为度量有关。