Cortical feedback and olfactory processing

皮质反馈和嗅觉处理

• 批准号: 10118416
• 负责人: VENKATESH N MURTHY
• 金额: $ 19.93万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10118416
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Anatomy; Area; Behavioral; Biological Markers; Brain; Code; Detection; Diagnosis; Diagnostic; Discrimination; Disease; Disease Progression; Etiology; Feedback; Functional disorder; Future; Human; Impairment; Link; Measures; Monitor; Morphology; Neurodegenerative Disorders; Odors; Olfactory Cortex; Olfactory Pathways; Pathology; Perception; Peripheral; Play; Property; Role; Sensory; Site; Smell Perception; Stimulus; Structure; Symptoms; Testing; experimental study; improved; in vivo; insight; interest; mouse model; multiphoton imaging; neural circuit; neural patterning; olfactory bulb; parent grant; public health relevance

Summary for the supplemental request Olfactory dysfunction is often a first symptom of several neurodegenerative diseases, including Alzheimer's disease (AD). Therefore, an improved understanding of how the neural circuitry and functional properties of the olfactory system are altered in models of AD may provide clues to the etiology of AD, as well as potential diagnostic readouts. In the olfactory system, feedback projections from the olfactory cortex to the olfactory bulb may play a critical role in both the detection and analytical processing of odor stimuli. These same projections may be particularly sensitive to AD progression due to their anatomical interface between the olfactory bulb and cortex, two sites of early disease progression. We will test the hypothesis that in a mouse model of AD, disease-related disruption of the morphology and stimulus coding properties of top-down projections to the olfactory bulb impairs olfactory function. In Supplemental Aim 1 we will monitor changes in morphological features of cortical projections to the olfactory bulb through AD-like progression. In Supplemental Aim 2 we will measure the functional properties of feedback projections using naturalistic odor stimuli, combined with in vivo multiphoton imaging and behavioral readouts. These aims are closely aligned with Parent Grant Aim 3, where we will measure the activity of cortical projections to the olfactory bulb to determine how these projections contribute to neural pattern separation and behavioral accuracy on naturalistic odor mixture tasks. The results of our supplemental studies will extend our understanding of the link between AD-like progression and olfactory impairment in two fundamental ways. First, we will gain new insight to the structure and function of long-range projections from the cortex to the olfactory bulb in the context of disease progression. Second, because olfactory dysfunction typically precedes the onset of other disease- related symptoms, we will begin to uncover the breakdown in stimulus coding that may predict a decline in perceptual accuracy that accompanies AD progression. The results we obtain from the completion of this project will provide the basis for future experiments related to plasticity and stimulus discrimination in the context of AD pathology.

补充请求的摘要 嗅觉功能障碍通常是几种神经退行性疾病的第一个症状，包括 阿尔茨海默氏病（AD）。因此，对神经电路和功能的如何提高了了解 AD模型中嗅觉系统的性质也会改变，也可能为AD的病因提供线索 作为潜在的诊断读数。在嗅觉系统中，反馈预测从嗅觉皮质到 嗅球在气味刺激的检测和分析过程中可能起关键作用。这些 由于它们的解剖界面之间的AD进展可能特别敏感 嗅球和皮层，这是早期疾病进展的两个部位。我们将在鼠标中测试以下假设 AD模型，与自上而下的形态和刺激编码特性的破坏和刺激的破坏 对嗅球的预测会损害嗅觉功能。在补充目标1中，我们将监视更改 通过类似广告的进展，对嗅球的皮层投影的形态特征。在 补充目标2我们将使用自然气味来衡量反馈预测的功能性能 刺激，结合体内多光子成像和行为读数。这些目标紧密地对齐 使用父授予AIM 3，我们将在其中测量对嗅球的皮质预测的活动 确定这些预测如何有助于神经模式分离和行为准确性 自然气味混合物任务。我们补充研究的结果将扩展我们对链接的理解 在类似广告的进展和嗅觉障碍之间以两种基本方式进行。首先，我们将获得新的见解 从皮质到嗅球的远程投影的结构和功能 疾病进展。其次，因为嗅觉功能障碍通常在其他疾病的发作之前 相关症状，我们将开始发现刺激编码的故障，这可能预测 伴随AD进展的感知准确性。我们从完成的结果中获得的结果 项目将为与可塑性和刺激歧视有关的未来实验提供基础 广告病理的背景。