Modulation of cortical processing by engagement with the sensory environment

描述(由申请人提供)：两个被呈现类似感官输入的人可能会以非常不同的方式处理输入的材料，这取决于他们对所呈现信息的参与程度。然而，人们还不知道参与(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。本研究的目的是利用小鼠模型研究参与对视觉输入大脑皮层加工的影响。首先，我们将建立一个实验准备，用于测量清醒的、头部固定的小鼠在执行行为任务时初级视觉皮质(V1)神经元的活动(目标1)。神经活动将通过双光子成像的视觉皮质神经元表达病毒传递的遗传编码的钙指示器(GCaMP5)，同时小鼠执行苛刻的方向辨别任务。响应装置将以交替的块被取出，以允许在参与和被动观看期间的响应进行比较。接下来，我们将使用在感兴趣的细胞类型(特别是副蛋白阳性和生长抑素阳性的中间神经元；目标2)中表达红色荧光蛋白(TdTomato)的转基因小鼠品系来表征参与对V1中不同类别神经元的影响。对中间神经元亚型的遗传鉴定将使我们能够剖析参与对皮质回路特定组件的影响。最后，我们会 研究参与对V1以上高级视觉皮层区域感觉加工的影响(目标3)。对于这些实验，将使用顺行示踪器识别次级视觉区域LM(外侧)、AL(前外侧)和PM(后内侧)，并使用GCAMP5进行成像。次级视觉区域的反应将被成像，以确定参与是否增强了感觉信息在整个视觉皮质层次中更广泛的传播。综上所述，这项工作将对理解行为参与对大脑皮层感觉加工的影响具有重要意义，并揭示困扰参与和注意的认知障碍的基本机制。

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 The response apparatus will be withdrawn in alternating blocks, allowing comparison of responses during engaged versus passive viewing.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.