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来源的输入如何影响视网膜信号传递到视觉皮层的丘脑中继，我们知道得很多。它们来自多种皮层下和皮层来源，构成丘脑中继细胞上的突触的主体，并作为调节因子影响视网膜回鞘信号传递的增益。上丘（SC）是一个主要的视网膜受体结构，它也向膝状背外侧核（dLGN）发送一个突出的投影，后者是向视觉皮层传递视网膜信号的一级核。然而，SC输入是否作为驱动因素帮助塑造dLGN中继神经元的接受野结构，或作为抑制或放大丘脑信息流的调节剂，仍未得到验证。为了了解SC产生的信息如何影响dLGN的功能，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构造通路的投影，光遗传学来光激活SC输入以唤起dLGN细胞的突触后活动，并在体外和体内记录技术来评估SC输入是dLGN活性的驱动者还是调节者。这些联合方法将使我们能够选择性地控制构造-膝部通路的神经元活动，并阐明两个视网膜受体皮层下结构之间的相互作用如何影响视觉信息的处理和传递。

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.