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.

补充请求摘要 嗅觉功能障碍通常是几种神经退行性疾病的首发症状，包括 阿尔茨海默病（AD）。因此，更好地理解神经回路和功能 在AD模型中嗅觉系统的特性改变也可能为AD的病因学提供线索， 作为潜在的诊断读数在嗅觉系统中，从嗅觉皮层到大脑皮层的反馈投射， 嗅球在气味刺激的检测和分析处理中可能起关键作用。这些 相同的投影可能对AD进展特别敏感，这是由于它们在AD和AD之间的解剖界面。 嗅球和皮层是疾病早期进展的两个部位。我们将测试一个假设， AD模型，自上而下的形态学和刺激编码特性的疾病相关破坏 向嗅球的投射损害嗅觉功能。在补充目标1中，我们将监测 通过AD样进展向嗅球的皮质投射的形态学特征。在 补充目标2我们将使用自然气味测量反馈投射的功能特性 刺激，结合体内多光子成像和行为读数。这些目标是紧密一致的 与父母格兰特目标3，在那里我们将测量皮质投射到嗅球的活动， 确定这些投射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大我们对这种联系的理解 AD样进展和嗅觉障碍之间的联系。首先，我们将获得新的见解 从皮层到嗅球的长程投射的结构和功能， 疾病进展。第二，因为嗅觉功能障碍通常先于其他疾病的发作- 相关的症状，我们将开始揭示刺激编码的崩溃，这可能预示着一个下降， 感知准确性伴随AD进展。我们完成这项工作所得到的结果是： 该项目将为未来与可塑性和刺激识别相关的实验提供基础。 AD病理学的背景。