Modulation of cortical processing by engagement with the sensory environment

描述（由申请人提供）：两个具有相似感官输入的个体可能会以非常不同的方式处理传入的材料，这取决于他们对所呈现信息的参与程度。然而，参与（定义为对感觉输入的非选择性注意）如何对神经处理产生如此强烈的影响尚不清楚。本研究的目的是利用小鼠模型研究接触对视觉输入皮层加工的影响。首先，我们将建立一个实验准备，用于测量执行行为任务的清醒、头部固定的小鼠初级视觉皮层（V1）神经元的活动（目的1）。神经活动将通过表达病毒传递的遗传编码钙指示剂（GCaMP5）的视觉皮质神经元的双光子成像来测量，同时小鼠执行要求高的方向识别任务。反应装置将在交替的块中取出，允许在参与和被动观看期间的反应进行比较。接下来，我们将使用在感兴趣的细胞类型（具体来说，parvalbumin阳性和生长抑素阳性的中间神经元）中表达红色荧光蛋白（TdTomato）的转基因小鼠系，表征参与对V1中不同类别神经元的影响；目的2)。中间神经元亚型的遗传鉴定将使我们能够解剖接触对皮层回路的特定组成部分的影响。最后，我们将

DESCRIPTION (provided by applicant): Two individuals presented with similar sensory input may process the incoming material in very different ways depending on their level of engagement with the presented information. However, it is not understood how engagement (defined as non-selective attention to sensory input) exerts such a strong influence on neural processing. The goal of the proposed research is to investigate the influence of engagement on cortical processing of visual input using a mouse model. First, we will establish an experimental preparation for measuring the activity of primary visual cortical (V1) neurons in awake, head-fixed mice performing a behavioral task (Aim 1). Neural activity will be measured by 2-photon imaging of visual cortical neurons expressing a virally delivered genetically encoded calcium indicator (GCaMP5) while the mouse performs a demanding orientation discrimination task. The response apparatus will be withdrawn in alternating blocks, allowing comparison of responses during engaged versus passive viewing. Next, we will characterize the effects of engagement on different classes of neurons in V1 using transgenic mouse lines that express red fluorescent protein (TdTomato) in cell types of interest (specifically, parvalbumin-positive and somatostatin- positive interneurons; Aim 2). Genetic identification of interneuron subtypes will allow us to dissect the effect of engagement on specific components of the cortical circuitry. Finally, we will investigate the impact of engagement on sensory processing in higher visual cortical regions beyond V1 (Aim 3). For these experiments, secondary visual areas LM (lateromedial), AL (anterolateral), and PM (posteromedial) will be identified using anterograde tracers and imaged using GCaMP5. Responses in secondary visual areas will be imaged to determine whether engagement enhances the propagation of sensory information more broadly throughout the visual cortical hierarchy. Taken together, this work will have important implications for understanding the influence of behavioral engagement on sensory processing in the neocortex, and reveal fundamental mechanisms underlying disorders of cognition that afflict engagement and attention.