Linking cortical circuit computations to visual perception

修改项目摘要/摘要部分 大脑皮层是有意识感知的所在地。我们的目标是测试特定皮层细胞类型执行的计算如何导致特定的感知状态。在这里，我们将使用小鼠视觉皮层来确定对比度感知的细胞基础。对比度是一个基本的刺激特性，整个视觉系统和增益控制机制，认为支持对比度知觉被破坏的各种神经精神疾病。因此，识别控制对比度感知的细胞类型是建立健康和疾病感知神经基础的关键步骤。在我们对视觉皮层神经元的初步细胞内记录中，我们发现对比度的增加会导致兴奋的短暂增加，然后是对网络兴奋性的长期抑制。我们的假设是，这种网络抑制是一种增益控制机制，是在局部抑制性中间神经元的控制下，并且对于确定感知对比度很重要。事实上，我们发现，在执行的对比度歧视任务，激活小白蛋白（PV）或生长抑素表达（SOM）抑制性中间神经元是足以减少感知的对比度的刺激所代表的操纵半球。为了测试在什么条件下PV和SOM细胞有助于获得控制和对比度感知，我们将使用生理和心理物理测量的组合。在目标1中，我们将使用全细胞和细胞外记录来确定驱动观察到的网络抑制的刺激特征（即对比度和大小）。然后，我们将使用光学和化学方法来确定哪些抑制性细胞类型负责在这些条件下驱动网络抑制。这将使分离的PV和SOM细胞在调节皮质增益的功能作用。在目标2中，我们将通过在对比度辨别任务期间抑制它们的活性来测试这些细胞类型对感知对比度的贡献。为了建立目标1中定义的电路机制与目标2中测量的感知效应之间的联系，我们将把驱动网络抑制的刺激条件纳入我们的对比度辨别任务。这将使我们能够比较PV和SOM细胞在刺激条件下对网络抑制和感知的操纵。总之，这些实验将把皮层计算和细胞类型归因于特定的感知状态。这将是将神经元的活动与感知联系起来的基本步骤，也是未来研究状态依赖性感觉处理机制的基础。

Modified Project Summary/Abstract Section The cortex is the seat of conscious perception. Our goal is to test how the computations performed by specific cortical cell types lead to specific perceptual states. Here, we will use the mouse visual cortex to determine the cellular basis of contrast perception. Contrast is a fundamental stimulus property represented throughout the visual system and the gain control mechanisms thought to support contrast perception are disrupted in a variety of neuropsychiatric disorders. Thus, identifying the cell types that control contrast perception is a critical step in establishing the neural basis of perception in both health and disease. In our preliminary intracellular recordings from neurons in the visual cortex, we find that increases in contrast drive a transient increase in excitation followed by a prolonged suppression of network excitability. Our hypothesis is that this network suppression is a gain control mechanism that is under the control of local inhibitory interneurons, and is important for determining perceived contrast. Indeed, we find that during performance of a contrast discrimination task, the activation of either parvalbumin- (PV) or somatostatin-expressing (SOM) inhibitory interneurons is sufficient to decrease perceived contrast of stimuli represented by the manipulated hemisphere. To test under what conditions PV and SOM cells contribute to gain control and contrast perception we will use a combination of physiological and psychophysical measurements. In Aim 1, we will use whole-cell and extracellular recordings to determine the stimulus features (i.e. contrast and size) that drive the observed network suppression. Then we will use opto- and chemo- approaches to determine which inhibitory cell types are responsible for driving network suppression under each of these conditions. This will enable dissociation of the functional roles of PV and SOM cells in regulating cortical gain. In Aim 2 we will test the contribution of these cell types to perceived contrast by suppressing their activity during a contrast discrimination task. To establish a link between the circuit mechanisms defined in Aim 1 and the perceptual effects measured in Aim 2, we will incorporate the stimulus conditions that drive network suppression into our contrast discrimination task. This will allow us to compare manipulation of PV and SOM cells on both network suppression and perception across stimulus conditions. Together, these experiments will ascribe cortical computations and cell types to specific perceptual states. This would be a fundamental step in linking the activity of neurons to perception, and the basis for future investigations of the mechanisms of state-dependent sensory processing.