Inhibitory regulation of cortical visual processing

描述(申请人提供)：GABA能抑制中间神经元被认为在调节大脑皮层正在进行的活动模式中发挥着强大的作用。根据中间神经元的内在属性、突触靶点和分子标志物的不同，中间神经元可以分为许多类。最大的两组是以胞体为靶点的表达小白蛋白的中间神经元和以树突为靶点的表达生长抑素的中间神经元。确定这两种突触抑制来源调节感觉加工的机制是理解大脑活跃网络功能背后复杂的细胞相互作用的关键一步。然而，人们对这些细胞的活动模式或影响知之甚少 在清醒的时候。利用初级视觉系统作为模型系统，我们将记录清醒的、运动的动物体内许多兴奋性和抑制性神经元的活动。利用已识别神经元的密集细胞外记录，我们将检查感觉刺激引起的神经元间募集的时间模式以及这些活动模式的对比度依赖性。我们将使用细胞内记录和特定细胞类型的光遗传操作相结合的方法来测试小白蛋白和生长抑素中间神经元对其突触后靶兴奋性神经元的输入整合和尖峰产生的影响。抑制被认为在促进皮层网络的功能灵活性和允许神经元输出的自适应缩放以匹配周围感觉环境中存在的输入范围方面发挥着重要作用。为了了解抑制性中间神经元在调节局部皮质网络的输入-输出关系中所起的动态作用，我们将测试小白蛋白和生长抑素中间神经元以及兴奋性神经元在调节皮层对视觉刺激反应的敏感性或增益方面的影响。我们将进一步测试抑制增益调制的行为状态依赖关系。这些研究将揭示清醒大脑中视觉处理的基本机制，并导致对皮质网络功能的更全面的了解。我们的实验结果将回答有关关键中间神经元群体的基本问题，这些群体在历史上不可能在体内靶向。由于输入积分和增益控制是神经函数的全局元素，因此我们的结果将是适用的 并将阐明对信息编码、感知和行为至关重要的皮质回路的功能和功能障碍。

DESCRIPTION (provided by applicant): GABAergic inhibitory interneurons are thought to play a powerful role in regulating the ongoing pattern of activity in the cortex. Interneurons can be divided into many classes based on their intrinsic properties, synaptic targets, and molecular markers. The two largest groups are the parvalbumin-expressing interneurons that target the soma and the somatostatin-expressing interneurons that target the dendrites. Identifying the mechanisms by which these two sources of synaptic inhibition regulate sensory processing is a critical step towards understanding the complex cellular interactions underlying active network function in the brain. However, little is known about the activity pattern or impact of these cells during wakefulness. Using the primary visual system as a model system, we will record the activity of many excitatory and inhibitory neurons in awake, moving animals. Using dense extracellular recordings of identified neurons, we will examine the temporal pattern of interneuron recruitment by sensory stimuli and the contrast-dependence of those activity patterns. We will use a combination of intracellular recordings and cell type-specific optogenetic manipulations to test the impact of parvalbumin and somatostatin interneurons on input integration and spike generation by their postsynaptic target excitatory neurons. Inhibition is thought to play a major role in facilitating the functional flexibility of cortical networks and allowing adaptive scaling of neuronal output to match the range of inputs present in the surrounding sensory environment. To understand the dynamic role that inhibitory interneurons play in regulating the input-output relationship of local cortical networks, we will test the impac of parvalbumin and somatostatin interneurons, as well as excitatory neurons, in modulating the sensitivity, or gain, of cortical responses to visual stimuli. We will further test the behavioral tate dependence of inhibitory gain modulation. These studies will reveal fundamental mechanisms of visual processing in the awake brain and lead to a more complete understanding of cortical network function. Results from our experiments will answer fundamental questions about key interneuron populations that have historically not been possible to target in vivo. Because input integration and gain control are global elements of neural function, our results will be applicable to systems throughout the brain and will elucidate the function and dysfunction of cortical circuits critical for information encoding, perception, and behavior.