Prefrontal Neuronal Responses During Extinction of Fear

恐惧消退过程中前额叶神经元的反应

• 批准号: 6538364
• 负责人: Mohammed R Milad
• 金额: $ 2.61万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6538364
• 关键词: albino rat; auditory stimulus; behavioral /social science research tag; behavioral extinction; biological models; brain electrical activity; cell population study; controlled environment chamber; environment; fear; histology; memory; microelectrodes; model design /development; neural information processing; neural transmission; neurons; neuropsychological tests; neuropsychology; prefrontal lobe /cortex; single cell analysis; statistics /biometry

DESCRIPTION: (Adapted from applicant?s abstract): A commonly used animal model of anxiety disorders is fear conditioning. In this paradigm, a neutral stimulus such as tone is paired with an aversive stimulus such as footshock. This pairing induces fearful responses to the tone. Following acquisition of fear conditioning, subsequent presentations of the tone cause fear responses to extinguish. Failure to extinguish fear has been proposed as a basis for anxiety disorders such as post-traumatic stress disorder (PTSD). The medial prefrontal cortex (mPFC) has been implicated in extinction. We recently showed that lesions of the vmPFC did not affect extinction over short time intervals, but blocked the recall of extinction after a 24-hour delay. There are two hypotheses that could explain the role of the vmPFC in recall of extinction: 1) VmPFC could be involved in signaling an inhibitory association between CS and US during extinction recall. 2) Alternatively, vmPFC could be signaling the extinguished context. Previous work has shown that in order to express extinction, rats must recall the context where extinction learning took place. To distinguish between these hypotheses, single-unit activity in the vmPFC will be recorded using tetrodes during fear conditioning. Tone-evoked responses as well as spontaneous activity will be recorded before and after extinction. Hypothesis 1: if the vmPFC were involved in signaling an inhibitory association between the CS and the US, tone-evoked responses of vmPFC neurons would change during extinction. Hypothesis 2: if the vmPFC were signaling extinguished contexts, a change in spontaneous firing rate during or after extinction would be expected. This proposed study will bring us closer to understanding the mechanisms of fear extinction. Facilitation of extinction processes in patients with disorders such as PTSD could potentially help in curing such disorders.

描述：（改编自申请人的摘要）：一种常用的动物模型 焦虑症是恐惧调节。在此范式中，中性刺激 诸如音调与厌恶刺激（例如脚印）配对。这 配对会引起对语气的恐惧回应。收购恐惧之后 调理，随后的语调演示导致恐惧回应 熄灭。已经提出了未能消除恐惧作为焦虑的基础 诸如创伤后应激障碍（PTSD）等疾病。内侧前额叶 皮质（MPFC）与灭绝有关。我们最近表明 VMPFC的病变不会在短时间间隔内影响灭绝，而是 24小时延迟后，阻止了灭绝的召回。有两个 可以解释VMPFC在灭绝灭绝中的作用的假设：1） VMPFC可能参与信号表明CS和 我们在灭绝期间。 2）或者，VMPFC可以发出信号 熄灭的上下文。以前的工作表明，为了表达 灭绝，大鼠必须回忆起发生灭绝学习的上下文。 为了区分这些假设，VMPFC中的单单元活动将 在恐惧调节过程中使用四极管记录。音调诱发的回应 以及自发活动将在灭绝之前和之后记录。 假设1：如果VMPFC参与信号抑制缔合 在CS和美国之间，VMPFC神经元的音调诱发反应会改变 在灭绝期间。假设2：如果VMPFC发出信号熄灭 上下文，在灭绝期间或之后自发发射速率的变化将会发生变化 可以预料。这项拟议的研究将使我们更加了解 恐惧灭绝的机制。促进患者的灭绝过程 伴随PTSD等疾病可能有助于治愈此类疾病。