Visual System Organization and Development

描述（由申请人提供）：拟进行的研究的主要目的是阐明丘脑控制灵长类大脑皮层加工的超微结构和功能机制。为了了解早期视觉皮层网络的功能，重要的是要认识到哪些回路致力于传达主要信息，哪些回路调节这些信息以及如何调节这些信息。我们对这一提议的具体论点是，所有的丘脑核都包含一些细胞群，这些细胞群作为驱动者，一些细胞群作为多个皮质区域的调节剂，从而介导一系列不同功能的产生。丘脑不仅仅是大脑皮层的被动中继。相反，正如初级视觉皮层（V1）依赖于LGN一样，次级视觉区（V2）和中颞叶视觉区（MT）依赖于通过丘脑（例如，pulvinar）的专用通路和V1的直接前馈连接的组合。具体来说，我们的假设是：(1)V1和pulvinar都是V2和MT中特定功能细胞群的驱动因素；(2)除了V2和MT是V1的调节剂外，pulvinar还作为V1的调节剂。这种安排允许通过动态循环在丘脑和皮层水平上出现新的特性。从LGN到V1的驱动因素的解剖轴突特征是已知的，但不知道这些特征是否可以推广到外皮层区域。我们将在pulvino- V2和V1-V2轴突（AIM1）上检查这些光显微和超微结构特征。我们将研究pulvinar是否为V2和MT细胞群提供了主要的功能驱动（Aim 2），并为V1提供了主要的调节输入（Aim3）。最后，我们将研究pulvinar是否不仅仅是一个中继，而是将来自不同途径的信息结合起来，在其内部合成复杂的功能（Aim 4）。在包括精神分裂症和阿尔茨海默病在内的严重精神疾病中，枕状核表现出较低的代谢，体积较小，神经元较少。了解枕状核的正常功能将有助于了解这些疾病中一些视觉功能障碍的原因。公共卫生相关性：在人类进化过程中，与物体识别和复杂运动有关的视觉脑区是大脑中扩大最多的区域之一。其中的一个区域，即脑后脑区，最近被发现在阿尔茨海默氏症中受到严重影响，也与精神分裂症的某些方面有关，但人们对这个区域的作用知之甚少。这个项目的目标是了解枕核的功能及其对视觉皮层的贡献。

Description (provided by applicant): The major goal of the proposed research is to elucidate the ultrastructural and functional mechanisms by which the thalamus controls cortical processing in the primate brain. In order to understand how early visual cortical networks function, it is important to recognize which circuits are dedicated to communicating the main message, which circuits regulate this message and how. Our specific thesis for this proposal is that all thalamic nuclei contain some cell groups that act as drivers and some that act as modulators for multiple cortical areas, thus mediating the generation of an array of diverse functions. The thalamus is not simply a passive relay to cortex. Instead, just as primary visual cortex (V1) depends on LGN, the secondary visual area (V2) and the middle temporal visual area (MT) depend on a combination of dedicated pathways through the thalamus (e.g., pulvinar) and direct feedforward connections from V1. Specifically, our hypothesis is that (1) both V1 and pulvinar act as drivers for specific functional cell groups in V2 and MT and (2) in addition to V2 and MT being modulators of V1, the pulvinar also acts as a modulator for V1. This arrangement allows new properties to emerge at both the thalamic and cortical levels through dynamic loops. Anatomical axonal signatures for drivers from LGN to V1 are known but it is not known if these signatures generalize to extrastriate cortical areas. We will examine for these light microscopic & ultrastructural signatures on pulvino- V2 and V1-V2 axons (AIM1). We will investigate whether the pulvinar provides a major functional drive for cell groups in V2 and MT (Aim 2) and a major modulatory input to V1 (Aim3). Finally, we will examine whether the pulvinar is much more than a mere relay and combines information from different pathways to synthesize complex functions within itself (Aim 4). In severe mental disorders including schizophrenia and Alzheimer's disease, the pulvinar exhibits lower metabolism, has smaller volume and fewer neurons. Understanding the normal functioning of pulvinar will shed light on the cause of some visual dysfunctions in these diseases. PUBLIC HEALTH RELEVANCE: Visual brain areas that are concerned with object recognition and complex motion are among the brain regions that have enlarged the most during the course of human evolution. One of these areas, the pulvinar, has recently been found to be severely affected in Alzheimer's disease and also to be involved in aspects of schizophrenia, yet very little is known about what this area does. The goal of this project is to understand the function of the pulvinar and its contribution to visual cortex.