Linking cortical circuit computations to visual perception

将皮质电路计算与视觉感知联系起来

• 批准号: 10570888
• 负责人: LINDSEY L GLICKFELD
• 金额: $ 44.02万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10570888
• 关键词: Acute; Animals; Automobile Driving; Behavioral; Cells; Conscious; Discrimination; Disease; Dissociation; Etiology; Functional disorder; Future; Genetic; Glutamate Receptor; Goals; Health; Interneurons; Intervention; Investigation; Lead; Link; Measurement; Measures; Mediating; Monitor; Mus; Neurons; Parvalbumins; Perception; Performance; Pharmaceutical Preparations; Physiological; Process; Property; Psychophysics; Pyramidal Cells; Role; Schizophrenia; Sensory; Shapes; Somatostatin; Source; Stimulus; Synapses; System; Testing; Visual; Visual Cortex; Visual Perception; Visual System; area striata; autism spectrum disorder; cell cortex; cell type; contextual factors; design; experimental study; extracellular; neural; neuropsychiatric disorder; optogenetics; pharmacologic; public health relevance; recruit; visual stimulus

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.

修改的项目摘要/摘要部分 皮层是有意识的所在地。我们的目标是测试特定皮质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。对比是整个视觉系统中代表的基本刺激特性，并且被认为支持对比感知的增益控制机制在各种神经精神疾病中被破坏。因此，确定控制对比感知的细胞类型是建立健康和疾病感知基础的关键步骤。在视觉皮层中神经元的初步细胞内记录中，我们发现对比度增加了激发的瞬时增加，然后长期抑制了网络兴奋性。我们的假设是，该网络抑制是一种受到局部抑制性中间神经元控制的增益控制机制，对于确定感知的对比很重要。确实，我们发现，在执行对比歧视任务时，白细胞蛋白（PV）或表达生长抑素的（SOM）抑制性中间神经元的激活足以减少由操纵半球表示的刺激的感知对比。为了在哪些条件下测试PV和SOM细胞有助于获得控制和对比感知，我们将结合生理和心理物理测量。在AIM 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每种情况下驱动网络抑制。这将使PV和SOM细胞在调节皮质增益中的功能作用。在AIM 2中，我们将通过在对比度歧视任务中抑制其活性来测试这些细胞类型对对比的贡献。为了在AIM 1中定义的电路机制与AIM 2中测得的感知效应之间建立联系，我们将纳入将网络抑制的刺激条件纳入我们的对比歧视任务中。这将使我们能够在刺激条件下对网络抑制和感知进行对PV和SOM细胞的操纵。这些实验将皮质计算和细胞类型归功于特定的感知状态。这将是将神经元的活性与感知联系起来的基本步骤，也是对国家依赖性感觉处理机制的未来研究的基础。