Cortical Processing

皮质处理

• 批准号: 8803774
• 负责人: Donald A Wilson
• 金额: $ 32.13万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803774
• 关键词: Aging; Amygdaloid structure; Animals; Anosmia; Anterior; Arousal; Attention; Autistic Disorder; Back; Behavioral; Brain; Cells; Central Nervous System Diseases; Code; Cognition Disorders; Complex; Congenital Disorders; Data; Detection; Discrimination; Disease; Equilibrium; Event; Feedback; Functional Magnetic Resonance Imaging; Funding; Health; Hippocampal Formation; Hippocampus (Brain); Human; Impairment; Label; Lateral; Left; Lesion; Limbic System; Longevity; Memory; Molds; Neurons; Noise; Odors; Olfactory Cortex; Olfactory Pathways; Pathway interactions; Pattern; Perception; Perceptual Disorders; Perceptual learning; Performance; Persons; Play; Process; Rest; Role; Sampling; Schizophrenia; Sensory; Sensory Physiology; Sensory Process; Shapes; Signal Transduction; Smell Perception; Source; Stimulus; Structure; System; Taste Perception; Techniques; Temporal Lobe; Testing; Training; Work; awake; base; behavioral outcome; cell type; disorder prevention; entorhinal cortex; expectation; experience; hedonic; in vivo; innovation; multi-electrode arrays; multisensory; neocortical; novel; object recognition; olfactory bulb; optogenetics; piriform cortex; receptive field; sensory discrimination

DESCRIPTION (provided by applicant): Cortical processing of sensory information plays a critical role in sensory discrimination, object recognition and memory. Cortical sensory processing has been shown to be highly dynamic, with past experience, current context and expectations shaping how the world is perceived on a moment by moment basis. Disorders of sensory processing constitute a major component of impairments induced by CNS disease and aging, as well as congenital disorders such as schizophrenia and autism. A largely overlooked aspect of odor processing is the role of top-down inputs in shaping olfactory cortical activity based on past-experience, expectation and context. Here we propose to explore the role of the lateral entorhinal cortex (LEC) in both odor processing and top-down control of piriform cortex (PCX ) and olfactory bulb. The LEC is both a component of the olfactory cortex (receives direct input from the olfactory bulb) and is a major component of the temporal lobe/limbic system memory circuitry as the primary afferent to the hippocampal formation. Importantly, the LEC also sends a strong projection back to the PCX and olfactory bulb - a pathway not well understood. There are three specific aims, each supported by new preliminary data, that test novel, specific hypotheses about the function of LEC in olfaction. In Specific Aim 1 we will extend our initial work showing significantly more selective single-unit odor receptive fields in LEC compared to PCX. First we will use in vivo intracellular recording in anesthetized animals to allow odor RF characterization of identified LEC cell types, and second we will compare single-unit and ensemble odor evoked activity in the awake, freely moving LEC and PCX to novel and familiar odors. These data will be the first to characterize olfactory sensory physiology of this region of olfactory cortex, and test our hypothesis that odor coding becomes more precise, in an experience-dependent manner, in this neocortical component of the olfactory cortex. In Aim 2, using optogenetic and reversible lesion techniques we will extend our preliminary data to test the hypothesis that LEC feedback to PCX functions in a highly cell specific manner to shape both PCX neuron odor RF's and temporal structure of PCX activity. This top-down influence may contribute to both perceptual acuity and odor memory as tested in Aim 3. In Aim 3 we will extend our preliminary data in awake, freely moving animals performing odor discrimination tasks to test our hypothesis that LEC top-down input shapes odor acuity both by modulating ongoing PCX odor-evoked activity and by contributing to anticipatory PCX single-unit and ensemble activity, prior to odor onset. Each Aim uses innovative concepts and techniques to test specific hypotheses regarding the role of a structure that serves not only as a component of the olfactory cortex, but also as a critical component of temporal lobe memory circuits.

描述（由申请人提供）：感觉信息的皮层处理在感觉辨别、物体识别和记忆中起着关键作用。大脑皮层的感觉处理被证明是高度动态的，过去的经验，当前的背景和期望塑造了世界是如何被感知的。感觉处理障碍是中枢神经系统疾病和衰老以及先天性疾病如精神分裂症和自闭症引起的损伤的主要组成部分。气味处理的一个很大程度上被忽视的方面是自上而下的输入在根据过去的经验，期望和背景塑造嗅觉皮层活动中的作用。在这里，我们建议探讨的作用，外侧内嗅皮层（LEC）的气味处理和自上而下的控制梨状皮质（PCX）和嗅球。LEC既是嗅觉皮质的组成部分（接收来自嗅球的直接输入），也是颞叶/边缘系统记忆回路的主要组成部分，作为海马结构的主要传入神经。重要的是，LEC还向PCX和嗅球发送强烈的投射-这是一种尚不清楚的途径。有三个具体的目标，每一个新的初步数据支持，测试新的，具体的假设LEC在嗅觉中的功能。在具体目标1中，我们将扩展我们的初步工作，与PCX相比，LEC中的单个单位气味感受野具有更大的选择性。首先，我们将在麻醉动物体内使用细胞内记录，以允许识别LEC细胞类型的气味RF表征，其次，我们将比较清醒，自由移动LEC和PCX的单一单位和合奏气味诱发活动的新的和熟悉的气味。这些数据将是第一个表征嗅觉皮层这一区域的嗅觉感觉生理学，并测试我们的假设，气味编码变得更加精确，在经验依赖的方式，在这个新皮层组成部分的嗅觉皮层。在目标2中，使用光遗传学和可逆损伤技术，我们将扩展我们的初步数据来测试LEC反馈到PCX功能以高度细胞特异性方式来塑造PCX神经元气味RF和PCX活性的时间结构的假设。这种自上而下的影响可能有助于感知敏锐度和气味记忆，如目标3中所测试的。在目标3中，我们将扩展我们的初步数据在清醒的，自由移动的动物执行气味辨别任务，以测试我们的假设，LEC自上而下的输入形状气味敏锐度，通过调节正在进行的PCX气味诱发的活动，并有助于预期的PCX单单位和合奏活动，气味发作之前。每个目标使用创新的概念和技术来测试特定的假设，关于结构的作用，不仅作为嗅觉皮层的组成部分，而且作为颞叶记忆回路的关键组成部分。