CORTICAL PROCESSING OF OLFACTORY STIMULI

描述(改编自申请人的摘要) 习惯化是非联想记忆的一种简单形式，是一种常见的特征 感觉系统的特征是响应性下降 对重复的刺激。感觉习惯化允许过滤较少的 重大或可预测的事件而不是其他机制，例如 受体适应。感觉过滤障碍已被牵连 在自闭症等疾病状态下。本提案审查了 梨状皮质前叶的嗅觉习惯化机制 (APCX)。APCX是研究习惯性的理想模型系统，因为 其相对简单和描述良好的突触组织，以及 对其突触生理学的广泛了解。初步结果 证明APCX神经元比同时适应更快 记录了主嗅球的传入活动，而这 习惯化与传入突触效能的降低有关。 所提出的工作分为四个基本实验。第一个遗嘱 进一步描述APCX和主嗅球的气味习惯性， 并特别注意描述其时间进程和 气味专一性。特定的反应将与细胞相关 记录的细胞内充盈和成像的形态和定位 细胞。 第二个实验将进一步研究气味的突触关联。 通过测量脑内已识别突触的有效性来实现习惯化 APCX。(自#年以来取得的成果已经部分实现了这一目标 提交了申请，这表明减少了 在有气味习惯性的突触传入中。) 第三和第四个实验将测试气味的特定假说 结合细胞内记录和细胞内记录的反应可塑性 药理操控。第三个是专门针对 兴奋性降低在气味习服中的作用，尤其是LTD 通过NMDA受体介导。第四部分将考察 习惯性中的抑制增加，通过GABAA或 GABAB受体。总而言之，希望这些研究将提供 关于习惯化和习惯化机制的重要信息 嗅觉系统中信息处理的突触机制。

Description (adapted from applicant's abstract) Habituation, a simple form of nonassociative memory, is a common feature of sensory systems and is characterized as a decrease in responsiveness to repeated stimuli. Sensory habituation allows filtering of less significant, or predictable events than other mechanisms such as receptor adaptation. Disorders of sensory filtering have been implicated in disease states such as autism. The present proposal examines mechanisms of olfactory habituation in the anterior piriform cortex (aPCX). The aPCX is an ideal model system to study habituation because of its relatively simple and well described synaptic organization, and the extensive knowledge of its synaptic physiology. Preliminary results demonstrate that aPCX neurons habituate more rapidly than simultaneously recorded afferent activity from the main olfactory bulb, and that this habituation is associated with a decrease in afferent synaptic efficacy. The proposed work is divided into four basic experiments. The first will further describe odor habituation in the aPCX and main olfactory bulb, with particular attention paid to characterizing its time course and odor specificity. Specific responses will be correlated with cell morphology and location by intracellular filling and imaging of recorded cells. The second experiment will further examine synaptic correlates of odor habituation by measuring the efficacy of identified synapses within the aPCX. (This aim has already been partially met by results obtained since the application was submitted, that indicate that there is a decrease in synaptic afferents with odor habituation.) The third and fourth experiments will test specific hypotheses of odor response plasticity with a combination of intracellular recording and pharmacological manipulations. The third is specifically aimed at the role of decreased excitation in odor habituation, particularly LTD mediated through NMDA receptors. The fourth will examine the role of increased inhibition in habituation, produced through either GABAA or GABAB receptors. Together, it is hoped that these studies will provide important information into both the mechanisms of habituation and synaptic mechanisms of information processing in the olfactory system.