Functional relationships between visual cortex and thalamus

描述（由申请人提供）：我们将首先使用来自小鼠大脑的体外切片制剂来研究视觉系统中丘脑皮质在两个方向上的相互作用，重点研究皮层区域V1和V2以及丘脑核LGN和LP。然后，我们建议开发体内制剂来测试体外工作的假设。我们大量使用光遗传学结合其他刺激模式来激活特定通路，并使用单细胞记录和电流源密度分析来测量反应。我们对这两种不同的皮质丘脑投影的作用特别感兴趣。一个从第6层发出并反馈到支配该区域的丘脑核；我们推测其主要功能是通过多种互补机制抑制丘脑皮质传导。另一种来自第5层，以前馈方式组织，支配丘脑区域，而不支配皮质区域；我们假设这代表了一个跨丘脑、皮质-丘脑-皮层通路的启动，该通路与直接的皮质-皮层投射平行组织。最后，我们还将验证这些双重途径以巧合检测方式运行以控制信息流的假设。这可以提供关于皮层功能的更广泛的见解，特别是关于不同皮层区域可以根据行为需要动态合作的新证据。

DESCRIPTION (provided by applicant): We shall initially use in vitro slice preparations from the mouse brain to study thalamocortical interactions in both directions in the visual system, concentrating on cortical areas V1 and V2 and thalamic nuclei LGN and LP. We then propose to develop in vivo preparations to test hypotheses from the in vitro work. We make heavy use of optogenetics in combination with other stimulation paradigms to activate specific pathways and use both single cell recording and current source density analysis to measure responses. We are particularly interested in the role of the two distinct corticothalamic projections. One emanates from layer 6 and feeds back to the thalamic nucleus innervating that area; we hypothesize that its main function is to depress thalamocortical transmission by multiple complementary mechanisms. The other emanates from layer 5 and is organized in a feed forward fashion, innervating thalamic regions that do not innervate its cortical area; we hypothesize that this represents the initiation of a transthalamic, cortico-thalamo-cortical pathway organized in parallel with direct corticocortical projections. Finally, we shall also test he hypothesis that these dual pathways operate in a coincidence detection manner to control information flow. This could provide more general insights regarding cortical functioning, particularly with respect to new evidence that different cortical areas can dynamically cooperate depending on behavioral needs. PUBLIC HEALTH RELEVANCE: We must better understand visual information flow through the first few stages of cortical processing to begin to understand how pathology in these pathways leads to vision loss including defects in cognitive visual functions, such as selective attention and object recognition. This could also lead to insights into disorders such as schizophrenia, which shows deficits in the sort of corticothalamic relationships we propose to study.