CORTICAL PROCESSING OF OLFACTORY STIMULI

描述（改编自申请人摘要） 习惯化是非联想记忆的一种简单形式， 感觉系统的反应能力下降， 重复的刺激。感官习惯允许过滤较少的 重要的或可预测的事件，而不是其他机制， 受体适应感觉过滤障碍与 在自闭症等疾病状态中。本提案审查了 梨状前皮质的嗅觉习惯化机制 （aPCX）。aPCX是研究习惯化的理想模型系统， 它的突触组织相对简单，描述得很好， 对突触生理学的广博知识初步结果 证明aPCX神经元比同时适应更快， 记录了来自主嗅球的传入活动， 习惯化与传入突触功效的降低有关。 拟议的工作分为四个基本实验。第一个将 进一步描述了aPCX和主要嗅球中的气味习惯化， 特别注意其时间进程的特点， 气味特异性特异性反应将与细胞 通过记录的细胞内填充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相关性 习惯化通过测量内识别的突触的功效， APCX。(This自2000年以来取得的成果已经部分实现了这一目标， 提交的申请表明， 在突触传入与气味习惯化。） 第三和第四个实验将测试气味的具体假设 反应可塑性与细胞内记录和 药理学操作。第三是专门针对 兴奋减少在气味习惯化中的作用，特别是LTD 通过NMDA受体介导。第四节将审查 习惯化抑制增加，通过GABAA或 GABAB受体。希望这些研究将为 重要的信息进入习惯化的机制， 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.