Cortical Processing

皮质处理

• 批准号: 8439070
• 负责人: Donald A Wilson
• 金额: $ 34.2万
• 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 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8439070
• 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; Hippocampal Formation; Hippocampus (Brain); Human; Impairment; Label; Lateral; Left; Lesion; Limbic System; Longevity; Memory; Molds; Neurons; Noise; Odors; Olfactory Cortex; Outcome; 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; cell type; disorder prevention; entorhinal cortex; expectation; experience; hedonic; in vivo; innovation; multisensory; neocortical; novel; object recognition; olfactory bulb; optogenetics; piriform cortex; public health relevance; 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(申请人提供)：感觉信息的皮质处理在感觉辨别、物体识别和记忆中起着关键作用。大脑皮层的感觉处理已被证明是高度动态的，过去的经验、当前的背景和预期塑造了人们在一瞬间如何感知世界。感觉加工障碍是中枢神经系统疾病和衰老以及精神分裂症和自闭症等先天性疾病引起的损害的主要组成部分。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、预期和背景塑造嗅觉皮质活动方面所起的作用。在这里，我们建议探索外侧内嗅皮层(LEC)在气味处理和梨状皮质(PCX)和嗅球自上而下控制中的作用。LEC既是嗅皮层的组成部分(接受嗅球的直接输入)，又是颞叶/边缘系统记忆电路的主要组成部分，是海马结构的初级传入。重要的是，LEC还向PCX和嗅球发出强烈的投射--这是一条尚未被很好理解的途径。有三个特定的目标，每个目标都得到了新的初步数据的支持，这三个目标测试了关于LEC在嗅觉中的功能的新的、特定的假设。在具体目标1中，我们将扩展我们的初步工作，显示与PCX相比，LEC中的单单位气味感受区具有明显更多的选择性。首先，我们将使用麻醉动物体内的细胞内记录来确定已识别的LEC细胞类型的气味RF特征，其次，我们将比较清醒、自由移动的LEC和PCX与新的和熟悉的气味的单个和整体气味诱发活动。这些数据将首次描述嗅觉皮质这一区域的嗅觉生理学特征，并检验我们的假设，即气味编码在嗅皮层的这一新皮质成分中以一种依赖经验的方式变得更加精确。在目标2中，使用光遗传和可逆损伤技术，我们将扩展我们的初步数据，以测试LEC反馈到PCX功能的假设，以高度细胞特异性的方式塑造PCX神经元气味RF和PCX活动的时间结构。这种自上而下的影响可能有助于感知敏锐度和气味记忆，如在目标3中测试的那样。在目标3中，我们将在执行气味识别任务的清醒、自由移动的动物中扩展我们的初步数据，以测试我们的假设，即LEC自上而下的输入通过调节正在进行的PCX气味诱发活动和通过在气味开始之前促进预期的PCX单位和整体活动来塑造气味敏锐度。每个目标都使用创新的概念和技术来测试关于结构角色的特定假设，该结构不仅是嗅觉皮质的组成部分，也是颞叶记忆电路的关键组成部分。