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。该项目将启动一项研究计划，以研究抑制性经典条件反射的神经机制。为了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，我们将在实验中使用眨眼条件反射制剂。特异性目的1的实验将通过兴奋毒性损伤、单位记录和可逆失活来研究小脑皮层在条件抑制中的作用。在Specific Aim 2的实验中，药物失活将用于评估神经回路中几个可能的位点在条件抑制获得中的作用，这些位点是兴奋性眨眼条件反射获得和表达的基础。Specific Aim 3的实验将确定条件抑制是否涉及不同于介导兴奋性条件反射的神经系统。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。提出的研究项目将为确定抑制性经典条件反射的神经机制提供重要的初步步骤。对抑制性经典条件反射的神经机制的成功分析可能会导致将这种实验方法应用于研究发生在其他学习情境中的兴奋性和抑制性过程。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，这些疾病涉及行为抑制缺陷。

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.