Amygdaloid Function in Fear Conditioning

杏仁核在恐惧调节中的功能

• 批准号: 6901449
• 负责人: Stephen Maren
• 金额: $ 17.34万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6901449
• 关键词: amygdala; association learning; auditory stimulus; avoidance behavior; behavior test; behavioral /social science research tag; behavioral extinction; conditioning; electrostimulus; experimental brain lesion; fear; laboratory rat; memory; neural information processing; neural plasticity; paired stimuli; performance

DESCRIPTION (provided by applicant): Pavlovian fear conditioning is a ubiquitous form of learning that may underlie disorders of fear and anxiety in humans. Many studies indicate that nuclei in the amygdala including the basolateral complex (BLA) and the central nucleus (CEA) are required for both the acquisition and expression of fear conditioning in mammals. Notably, neurons in both areas exhibit learning-related increases in spike firing during fear conditioning and pharmacological inhibition of both regions reduces fear conditioning. This suggests a role for BLA and CEA neurons in elaborating memories of aversive experiences, although the precise function of these areas in Pavlovian fear conditioning remains unclear. In the present proposal, it is hypothesized that BLA and CEA neurons encode distinct associative representations during fear conditioning. More specifically, we suggest that BLA neurons encode CS-US (S-S) representations that are sensitive to the current value of the US, whereas CEA neurons encode CS-CR (S-R) associations that are insensitive to US value. Moreover, we hypothesize that the relative contribution of these associations, and hence the BLA and CEA, to conditional fear varies as a function of training. To exam these hypotheses, we will use single-unit recordings, reversible pharmacological lesions and sophisticated behavioral designs to isolate the function of amygdala neurons in fear memory processes. The first specific aim will use inflation and devaluation procedures to examine the role of BLA and CEA neurons in representing US "value", which will be indexed by measuring conditional freezing to an auditory CS that has been paired with an aversive US. The second aim will examine the associative basis (S-S or S-R) for conditional fear after overtraining. The third aim will examine whether the role for synaptic plasticity in the BLA and CEA changes as a function of training. Collectively, these experiments represent the first systematic attempt to define parallel, associative functions of BLA and CEA neurons in aversive conditioning. The outcome of these experiments will have an important impact on current conceptions of both amygdaloid function and on clinical disorders of fear that depend on emotional learning and memory.

描述（由申请人提供）：帕夫洛夫恐惧条件是一种无处不在的学习形式，可能是人类恐惧和焦虑症的基础。 许多研究表明，杏仁核中的核包括基底外侧复合物（BLA）和中央核（CEA）（CEA）是哺乳动物中恐惧调节条件的获取和表达所必需的。 值得注意的是，这两个地区的神经元在恐惧调节和对两个区域的药理抑制期间均表现出与学习相关的峰值发射的增加，从而减少了恐惧调节。 这表明BLA和CEA神经元在阐述厌恶经历的记忆中发挥了作用，尽管这些领域在帕夫洛​​维亚恐惧条件中的确切功能尚不清楚。 在本提案中，假设BLA和CEA神经元在恐惧调节过程中编码不同的关联表示。 更具体地说，我们建议BLA神经元编码对美国当前值敏感的CS-US（S-S）表示，而CEA神经元编码对美国值不敏感的CS-CR（S-R）关联。 此外，我们假设这些关联的相对贡献以及BLA和CEA对有条件的恐惧随训练的函数而变化。 为了检验这些假设，我们将使用单单元记录，可逆的药理学病变和复杂的行为设计来隔离杏仁核神经元在恐惧记忆过程中的功能。 第一个具体目的将使用通货膨胀和贬值程序来检查BLA和CEA神经元在代表我们“值”中的作用，通过测量有条件的冻结，将其与与厌恶的美国配对一起索引。 第二个目的将检查过度训练后的有条件恐惧的关联基础（S-S或S-R）。 第三个目标将检查BLA和CEA中突触可塑性的作用是否随训练的函数而变化。 总的来说，这些实验代表了在厌恶条件下定义BLA和CEA神经元平行的，关联功能的首次系统尝试。 这些实验的结果将对杏仁酸功能的当前概念以及依赖情绪学习和记忆的恐惧症症状产生重要影响。