Functional relationships between visual cortex and thalamus

描述(申请人提供)：我们将首先使用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，主要集中在皮质V1和V2区域以及丘脑LGN和Lp核。然后，我们建议开发体内制剂来测试来自体外工作的假说。我们大量使用光遗传学与其他刺激范式相结合来激活特定的通路，并使用单细胞记录和电流源密度分析来测量反应。我们特别感兴趣的是这两个不同的皮质丘脑投射的作用。一种来自第六层，反馈到支配该区域的丘脑核；我们假设它的主要功能是通过多种互补机制抑制丘脑皮质的传递。另一个发自第5层，以前馈方式组织，支配不支配其皮质区域的丘脑区域；我们假设这代表着一条与直接皮质投射平行组织的跨丘脑、皮质-丘脑-皮质通路的启动。最后，我们还将检验这一假设，即这些双路径以符合检测的方式运行，以控制信息流。这可以提供更多关于皮质功能的一般性见解，特别是关于不同皮质区域可以根据行为需求动态合作的新证据。 与公共健康相关：我们必须更好地了解视觉信息流通过皮质处理的最初几个阶段，以开始了解这些通路中的病理如何导致视力丧失，包括认知视觉功能的缺陷，如选择性注意和物体识别。这也可能导致对精神分裂症等疾病的洞察，精神分裂症显示出我们计划研究的那种皮质-丘脑关系的缺陷。

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.