Tectal influences on visual thalamic activity: an optogenetic approach

描述（由申请人提供）：关于来自视网膜以外的来源的输入如何影响视网膜信号在通往视觉皮层的路径中的丘脑中继，已经知道很多。它们来源于皮层下和皮层，构成丘脑中继细胞上的大量突触，并作为调节剂影响视网膜神经节信号传递的增益。上级丘（SC）是初级视网膜接受结构，也向背外侧膝状体核（dLGN）发送突出的投射，背外侧膝状体核是将视网膜信号传递到视皮层的一级核。然而，SC输入是否作为一个驱动程序，以帮助塑造dLGN中继神经元的感受野结构或作为一个调制器，以抑制或放大丘脑信息流仍然未经测试。为了了解SC产生的信息如何影响dLGN功能以及特定的SC细胞类型如何对此做出贡献，我们将利用小鼠转基因来可视化或靶向细胞类型和顶盖神经元通路的投射，光遗传学来光激活SC输入以唤起dLGN细胞中的突触后活动，以及体外和体内记录技术，以评估SC输入是否表现为dLGN活性的驱动剂或调节剂。这些结合的方法将使我们能够选择性地控制顶盖膝状体通路的神经元活动，并阐明两个视网膜受体皮质下结构之间的相互作用如何影响视觉信息的处理和传递。 公共卫生相关性：这些研究将为丘脑一级感觉核团如何接受和处理外周感觉器官的信息提供有价值的信息。他们还将揭示如何传入输入从中央结构可以调节丘脑的信息流的路线感觉皮质区。利用光遗传学工具了解丘脑回路的功能和结构组织可能会进一步深入了解 对由于连接的不正常模式的形成而导致的神经系统紊乱的研究和治疗。

DESCRIPTION (provided by applicant): Much is known about how inputs from sources other than the retina affect the thalamic relay of retinal signals in route to the visual cortex. They arse from a variety of subcortical and cortical sources, comprise the bulk of synapses onto thalamic relay cells and act as modulators to affect the gain of retinogeniculate signal transmission. The superior collliculus (SC), a primary retino-recipient structure, also sends a prominent projection to the dorsal lateral geniculate nucleus (dLGN), the first order nucleus that conveys retinal signals to visual cortex. However, whether SC input acts as a driver to help shape the receptive field structure of dLGN relay neurons or as a modulator to dampen or amplify the flow of thalamic information remains untested. To understand how information arising from the SC influences dLGN function and how particular SC cell types contribute to this, we shall make use of mouse transgenics to visualize or target cell types and projections of the tectogeniculate pathway, optogenetics to photo-activate SC inputs to evoke postsynaptic activity in dLGN cells, and in vitro and in vivo recording techniques to assess whether SC inputs behave as drivers or modulators of dLGN activity. These combined approaches will allow us to selectively control the neuronal activity of the tecto-geniculate pathway and shed light on how interactions between two retino- recipient subcortical structures affect the processing and transfer of visual information. PUBLIC HEALTH RELEVANCE: These studies will provide valuable information about how first-order sensory nuclei of the thalamus receive and process information from peripheral sense organs. They shall also reveal how afferent input from central structures can modulate the flow of thalamic information in route to sensory cortical areas. Understanding the functional and structural organization of thalamic circuitry with optogenetic tools may offer further insight into the study and treatment of neurological disorders that result from the formation of abnormal patterns of connectivity.