Inhibitory regulation of cortical visual processing

描述（由申请人提供）：GABA能抑制性中间神经元被认为在调节皮质中持续的活动模式中起重要作用。中间神经元可以根据其内在特性、突触靶点和分子标记物分为许多类。最大的两组是靶向索马的表达小白蛋白的中间神经元和靶向树突的表达生长抑素的中间神经元。确定这两种突触抑制源调节感觉处理的机制是理解大脑中活跃网络功能背后复杂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。以初级视觉系统为模型系统，我们将记录清醒、运动的动物中许多兴奋性和抑制性神经元的活动。使用密集的细胞外记录确定的神经元，我们将检查的时间模式的感觉刺激和这些活动模式的对比度依赖性的interneuron招聘。我们将使用细胞内记录和细胞类型特异性光遗传学操作的组合来测试小清蛋白和生长抑素中间神经元对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起主要作用。为了了解抑制性中间神经元在调节局部皮层网络的输入-输出关系中发挥的动态作用，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的反应的敏感性或增益中的影响。我们将进一步测试抑制性增益调制的行为状态依赖性。这些研究将揭示清醒大脑中视觉处理的基本机制，并导致对皮层网络功能的更全面理解。我们的实验结果将回答关于关键的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，因此我们的结果是适用的 整个大脑的系统，并将阐明功能和功能障碍的皮质电路的信息编码，感知和行为的关键。

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.