Modulation of intrinsic excitability in mPFC neurons

mPFC 神经元内在兴奋性的调节

• 批准号: 7317344
• 负责人: DARAH Esther FONTANEZ
• 金额: $ 2.67万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-11-16 至 2009-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7317344
• 关键词: Action Potentials; Address; Agonist; Amygdaloid structure; Animals; Behavioral; Brain; Conditioned Stimulus; Emotions; Excitatory Amino Acid Antagonists; Extinction (Psychology); Fiber; Frequencies; Fright; Glutamate Receptor; Glutamates; Goals; In Vitro; Label; Lead; Measures; Medial; Mediating; Metabotropic Glutamate Receptors; Microspheres; Modeling; Neurons; Numbers; Phobic anxiety disorder; Post-Traumatic Stress Disorders; Prefrontal Cortex; Rattus; Research; Resistance; Shock; Slice; Stimulus; Synapses; Work; base; conditioned fear; day; in vivo; interest; learning extinction; neuromechanism; receptor; response

This proposal addresses a fundamental question in emotion research; can fear extinction be pharmacologically enhanced? Fear extinction is the decrease in fear responses that normally occurs when a conditioned stimulus like a tone is repeatedly presented in the absence of the unconditioned stimulus such as a shock. Our overall goal is to understand the neural mechanisms by which fear extinction can be enhanced. Although behavioral and in vivo electrophysiological studies implicate an increase in medial prefrontal cortex (mPFC) activity in fear extinction, nothing is known about the cellular mechanisms involved. Our current working hypothesis is that pharmacological enhancement of the intrinsic excitability of mPFC neurons projecting to the amygdala will lead to an increase in the recall of extinction. Because the mPFC projection to the amygdala is centralto our model of extinction expression, we will concentrate our efforts on mPFC neurons which are known to project to the amygdala. Aim 1 will examine the mechanisms by which the intrinsic excitability of mPFC neurons projecting to the amygdala can be enhanced in vitro through the stimulation of glutamate receptors. Aim 2 will determine whether intrinsic excitability of mPFC neurons is enhanced by svnaptic stimulation. Aim 3 will determine whether receptor agonists which enhance the intrinsic excitability of mPFC neurons in vitro enhance extinction learning. Because extinction-based exposure therapies are the main treatment for post-traumatic stress disorder (PTSD) and phobias, there is considerable interest in facilitating extinction with pharmacological agents.

该提案解决了情感研究中的一个基本问题。害怕灭绝是药理学 增强？恐惧灭绝是恐惧反应的减少，通常会在条件刺激的情况下发生 就像没有无条件的刺激（例如冲击）的情况下，反复呈现语调一样。我们的总体目标 是要了解可以增强恐惧灭绝的神经机制。虽然行为和 体内电生理研究暗示恐惧中内侧前额叶皮层（MPFC）活性增加 灭绝，对所涉及的细胞机制一无所知。我们目前的工作假设是 投射到杏仁核的MPFC神经元的内在兴奋性的药理增强 将导致灭绝召回的增加。因为对杏仁核的MPFC投影是中心 我们的灭绝表达模型，我们将精力集中在已知可以投射的MPFC神经元上 到杏仁核。 AIM 1将检查MPFC神经元内在兴奋性的机制 通过刺激谷氨酸受体，可以增强对杏仁核的投射。 AIM 2意志 确定MPFC神经元的固有兴奋性是否通过SVNAPTIC刺激增强。目标3意志 确定在体外增强MPFC神经元内在兴奋性的受体激动剂是否会增强 灭绝学习。因为基于灭绝的暴露疗法是创伤后压力的主要治疗方法 疾病（PTSD）和恐惧症，对促进药理学剂的灭绝引起了极大的兴趣。