Inhibitory regulation of cortical visual processing

皮质视觉处理的抑制性调节

• 批准号: 9058078
• 负责人: JESSICA A CARDIN
• 金额: $ 29.72万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9058078
• 关键词: Animals; Behavior; Behavioral; Biological Models; Biological Neural Networks; Brain; Cells; Complex; Data; Dendrites; Dependence; Electrophysiology (science); Elements; Environment; Epilepsy; Exhibits; Functional disorder; Generations; Goals; Health; In Vitro; Interneurons; Knowledge; Lead; Mediating; Methods; Neurons; Neurophysiology - biologic function; Output; Parvalbumins; Pattern; Perception; Play; Population; Process; Property; Recruitment Activity; Regulation; Role; Runaway; Sensory; Sensory Process; Somatostatin; Source; Synapses; System; Testing; Time; Visual; Visual Cortex; Visual system structure; Wakefulness; Work; area striata; awake; base; behavior test; brain cell; cell type; excitatory neuron; extracellular; flexibility; in vivo; inhibitory neuron; innovation; insight; molecular marker; nervous system disorder; neural circuit; neuronal cell body; novel; optogenetics; postsynaptic; prevent; research study; response; sensory input; sensory stimulus; spatiotemporal; synaptic inhibition; visual process; visual processing; visual stimulus

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.

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活动中持续的活动模式中起着强大的作用。神经元可以根据其内在特性，突触靶标和分子标记物分为许多类。这两个最大的组是针对soma的表达白蛋白的中间神经元和针对树突的表达生长抑素的中间神经元。确定这两种突触抑制作用来调节感觉处理的机制是了解大脑中主动网络功能的复杂细胞相互作用的关键步骤。但是，这些细胞的活动模式或影响知之甚少 在清醒期间。使用主要的视觉系统作为模型系统，我们将记录许多兴奋性和抑制性神经元在醒着的动物中的活性。使用鉴定神经元的密集细胞外记录，我们将通过感觉刺激和这些活性模式的对比依赖性检查中间神经元募集的时间模式。我们将结合细胞内记录和细胞类型特异性的光遗传学操纵来测试白蛋白和生长抑制素中间神经元对输入积分和尖峰产生的影响，并通过其突触后靶点兴奋性神经元产生。人们认为，抑制作用在促进皮质网络的功能灵活性方面起着重要作用，并允许神经元输出的自适应缩放与周围感觉环境中存在的输入范围相匹配。为了了解抑制性中间神经元在调节局部皮质网络的投入输出关系中起着的动态作用，我们将测试白蛋白蛋白和抑制性抑制素中间神经元的脱落，以及兴奋性神经元，以及调节对视觉刺激的敏感性或增益，对视觉刺激的敏感性或增益。我们将进一步测试抑制性增益调制的行为差异依赖性。这些研究将揭示清醒大脑中视觉处理的基本机制，并使对皮质网络功能有更全面的了解。我们实验的结果将回答有关关键中间神经元种群的基本问题，这些问题在历史上是不可能靶向体内的。由于输入集成和收益控制是神经功能的全球元素，因此我们的结果将适用 到整个大脑的系统，并将阐明对信息编码，感知和行为至关重要的皮质电路的功能和功能障碍。