Neural Mechanisms of Inhibitory Classical Conditioning

描述（由申请人提供）：抑制性条件反射是联想学习理论模型的核心组成部分，但其神经基础尚未完全阐明。条件抑制通常被认为是由于条件刺激（CS）和非条件刺激（US）之间的关联的发展。本计划将启动一项研究计划，以检查抑制性经典条件反射的神经机制。在这些实验中将使用眨眼条件反射制剂，以比较抑制性条件反射的神经机制与先前确定的兴奋性条件反射的神经机制。 具体目标1的实验将使用兴奋性毒性损伤、单位记录和可逆失活来研究小脑皮质在条件抑制中的作用。 在特定目标2的实验中，药理学失活将用于评估神经回路内几个可能位点在条件性抑制获得中的作用，这些位点是兴奋性眨眼条件性获得和表达的基础。 具体目标3的实验将确定条件抑制是否涉及与介导兴奋性条件反射的神经系统不同的神经系统。 抑制性学习的根本重要性强调了研究其神经机制的必要性。 拟议的研究项目将提供重要的初步步骤，以确定抑制性经典条件反射的神经机制。抑制性经典条件反射的神经机制的成功分析可能会导致这种实验方法的应用，在其他学习情况下发生的兴奋性和抑制性过程的研究。这些研究的结果也可能导致更好地理解与各种精神疾病相关的功能病理学，这些精神疾病涉及行为抑制的缺陷。

DESCRIPTION (provided by applicant): Inhibitory conditioning is a central component of theoretical models of associative learning but its neural basis has not been fully elucidated. Conditioned inhibition is generally thought to be due to the development of an association between a conditioned stimulus (CS) and the omission of an unconditioned stimulus (US). The proposed project will initiate a research program to examine the neural mechanisms of inhibitory classical conditioning. The eyeblink conditioning preparation will be used in these experiments in order to compare the neural mechanisms of inhibitory conditioning with the previously identified neural mechanisms of excitatory conditioning. The experiments of Specific Aim 1 will investigate the role of the cerebellar cortex in conditioned inhibition using excitotoxic lesions, unit recording, and reversible inactivation. In the experiments of Specific Aim 2, pharmacological inactivation will be used to assess the roles of several possible sites within the neural circuitry underlying the acquisition and expression of excitatory eyeblink conditioning in the acquisition of conditioned inhibition. The experiments of Specific Aim 3 will determine whether conditioned inhibition involves neural systems that are distinct from the neural systems that mediate excitatory conditioning. The fundamental importance of inhibitory learning underscores the need to study its neural mechanisms. The proposed research project will provide important initial steps toward determining the neural mechanisms of inhibitory classical conditioning. A successful analysis of the neural mechanisms of inhibitory classical conditioning may lead to the application of this experimental approach to the study of excitatory and inhibitory processes that occur in other learning situations. The results of these studies may also lead to a better understanding of the functional pathology associated with various psychiatric disorders that involve deficits in behavioral inhibition.