Neuronal ensembles in the rodent visual cortex

描述(申请人提供)：在感觉体验过程中，视网膜向大脑传输一系列不同的视觉信息。沿着皮质下和皮质通路的神经元必须迅速处理在世界上导航所必需的功能。我们的目标是了解远程大脑皮层连接的特殊性是如何将视觉信息分配到多个大脑皮层区域的，以及这些大脑皮层区域如何辅助上下文相关的感觉行为。视觉神经科学中的一个重要假设是，感觉信息被分离成平行的流，在这些流中，神经元亚群将轴突发送到专门处理不同视觉特征的皮质区域。对食肉动物和灵长类动物的研究已经发展出了这个重要的假说，但它的许多方面仍然没有得到测试，因为手头的工具不能在细胞水平上令人满意地解决这个问题。最近为小鼠开发的光学和遗传学工具有望改变对视觉皮质功能、其与潜在回路的关系以及它在行为中的作用的研究。我们目前的提议将建立一个小鼠模型，用于研究跨越多个皮质区域的视觉微电路，并开始描述它们之间的功能连接规则。我们已经发现，警觉小鼠初级视觉皮质(V1)神经元的感觉反应可以调节到广泛的空间和时间频率。这表明在视觉皮层加工的第一阶段存在丰富的视觉经验表征。我们的初步数据表明，两个较高的视觉区域编码了时间和空间频率的缩小和互补范围，这与基于并行处理的功能组织一致。在这项授权中，我们建议测量视觉皮层区域之间感受野特性的这种差异(目标1)，确定这种平行组织的基础电路(目标2)，并评估这些通路是否受到行为的不同调制(目标3)。这项工作将为将特定区域的计算与依赖于处理不同视觉特征的行为联系起来--例如对象识别和导航--提供基础。 公共卫生相关性：许多对公共健康影响最大的神经和精神疾病--阿尔茨海默病、中风、癫痫和自闭症--都是功能性疾病，可能与紊乱的大脑生理和连接有关。拟议的研究将以前所未有的分辨率和完整性表征大脑回路的生理学和连通性。我们开发的在数周和数月内对单个神经元进行长期监测的方法可以应用于功能性大脑疾病的小鼠模型，从而能够对疾病进展和治疗干预进行纵向研究。

DESCRIPTION (provided by applicant): During sensory experience, the retina transmits a diverse array of visual information to the brain. Neurons along subcortical and cortical pathways must rapidly process the features necessary for navigating through the world. Our goal is to understand how the specificity of long-range cortical connectivity underlies the distribution of visual information to multiple cortical areas, and how these cortical areas subserve context- dependent sensory behaviors. A major hypothesis in visual neuroscience is that sensory information is segregated into parallel streams, in which subpopulations of neurons send axons to cortical areas that are specialized to process distinct visual features. Studies in carnivores and primates have developed this important hypothesis, but many aspects of it remain untested because the tools at hand could not satisfactorily address this question at a cellular level. Recent optical and genetic tools developed for the mouse promise to transform the study of visual cortical function, its relationship to underlying circuitry, and its role in behavior. Our current proposal will establish a mouse model for studying visual microcircuitry across multiple cortical areas and begin to describe rules of functional connectivity between them. We have found that the sensory responses of neurons in the primary visual cortex (V1) of alert mice are tuned to a wide range of spatial and temporal frequencies. This suggests that there is a rich representation of visual experience at the first stage of visual cortical processing. Our preliminary data suggest that two higher visual areas encode reduced and complementary ranges of temporal and spatial frequencies, consistent with a functional organization based on parallel processing. In this grant, we propose to measure this divergence of receptive-fields properties between visual cortical areas (Aim 1), to determine the circuitry underlying this parallel organization (Aim 2), and to assess whether these pathways are differentially modulated by behavior (Aim 3). This work will provide the basis for linking area-specific computations to behaviors-- such as object recognition and navigation-- that rely on the processing of distinct visual features. PUBLIC HEALTH RELEVANCE: Many of the neurological and psychiatric diseases with the largest impact on public health-Alzheimer's disease, stroke, epilepsy, and autism-are functional disorders that likely have correlates in disordered brain physiology and connections. The proposed studies will characterize the physiology and connectivity of brain circuits with unprecedented resolution and completeness. The approaches we develop for chronic monitoring of individual neurons over weeks and months can be applied to mouse models of functional brain disorders, enabling longitudinal studies of disease progression and therapeutic interventions.