Layer 4 circuits and sensory processing

第 4 层电路和感觉处理

• 批准号: 10413008
• 负责人: Bernardo Rudy
• 金额: $ 40.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413008
• 关键词: Acetylcholine; Animals; Area; Arousal; Attention; Auditory area; Axon; Behavior; Behavioral; Cells; Cerebral cortex; Detection; Disease; Disinhibition; Electrophysiology (science); Exhibits; Interneurons; Intervention; Mediating; Mediator of activation protein; Membrane Potentials; Memory; Methods; Minority; Modality; Mus; Muscarinics; Myoepithelial cell; Natural Increases; Neocortex; Neuromodulator; Neurons; Output; Parvalbumins; Pattern; Perception; Performance; Population; Property; Rodent; Role; Sensory; Sensory Process; Signal Transduction; Slice; Somatosensory Cortex; Somatostatin; Specificity; System; Testing; Thalamic structure; Touch sensation; Training; Vibrissae; Visual Cortex; awake; barrel cortex; basal forebrain; cell type; cholinergic; expectation; experimental study; improved; in vivo; innovation; neuronal circuitry; neuroregulation; novel; response; sensory input; sensory mechanism; sensory signal detection; sensory stimulus; sensory system; signal processing; somatosensory; spatiotemporal

Abstract The neocortex generates a representation of the outside world by combining information from different sensory modalities and integrating this with internally generated information, such as memories and expectations. Furthermore, cortical processing and perception are contextually adjusted by the actions of neuromodulators released in the neocortex during specific behavioral states such as arousal and attention. In most sensory systems, sensory information enters the cortex through projections from the sensory thalamus that primarily target layer 4 (L4). Thus, the thalamocortical response transformations occurring in L4 start the cortical processing of sensory information that results in a sensory percept that is optimized for the behavioral needs of the animal. However, we still have an incomplete understanding of the transformations of sensory input that take place in L4 during behavior and the circuits mediating these transformations. This information is critical for a mechanistic understanding of sensory processing, which is necessary for interventions to treat diseases resulting from altered sensory perception. Cortical processing is mediated by dynamic microcircuits composed of excitatory or principal neurons (PNs), which transmit signals to other areas and a diverse array of inhibitory GABAergic interneurons (INs), which sculpt cortical circuits and are critical for signal processing. However, due to their diversity and low representation, recording IN activity during behavior and understanding their function has been challenging. This project uses an innovative approach (Channelrhodopsin-assisted patching), that facilitates the efficient targeted in vivo recording of specific cell types at any cortical depth, to advance our understanding of L4 circuits. The studies are focused on the two main IN populations in L4 of somatosensory cortex, the fast-spiking parvalbumin--expressing basket cells (PV INs) and the somatostatin-expressing INs (SST INs), which together account for 80-90% of L4 INs. Experiments in slices have led to the hypothesis that the function of L4 SST INs, which are major targets of cholinergic influence, is to regulate PV IN activity. L4 PV INs produce feedforward inhibition (FFI) of thalamocortical inputs and thereby control the feature selectivity of L4 PNs. This application will test the hypotheses that L4 SST INs regulate PV IN-mediated inhibition of PNs, and that the disinhibition of PNs produced in L4 as a result of the cholinergic activation of SST cells contributes to the mechanisms by which ACh enhances sensory detection. To investigate the disinhibition hypothesis, in Aim 1 we will study the changes in activity of L4 PV INs and PNs during behavioral states in which SST INs normally increase their activity and the effects of manipulating SST IN activity. In Aim 2, we will use a sensory detection task that depends on cholinergic modulation to investigate the role of L4 SST IN activity on touch responses, and the contribution of the muscarinic activation of SST INs to the cholinergic enhancement of sensory signals and behavioral performance.

抽象的 新皮层通过结合来自不同的信息来产生外界的代表 感官方式并将其与内部生成的信息（例如记忆和 期望。此外，皮质处理和感知是通过上下文调整的 在特定行为状态（如唤醒和注意力）中，在新皮层中释放的神经调节剂。 在大多数感官系统中，感觉信息通过感官的投影进入皮质 丘脑主要针对第4层（L4）。因此，发生在 L4启动了感官信息的皮质处理，从而导致感官感知被优化 动物的行为需求。但是，我们仍然对 行为期间在L4中发生的感觉输入的转换和介导的电路 转型。此信息对于对感官处理的机械理解至关重要，这是 干预措施以治疗因感觉知觉改变而导致的疾病所必需的。皮质加工 由由兴奋性或主神经元（PNS）组成的动态微电路介导 向其他区域以及各种抑制性GABA能中间神经元（INS）的信号，雕刻皮质 电路，对于信号处理至关重要。但是，由于它们的多样性和较低的代表性， 在行为和理解其功能过程中的活动记录一直具有挑战性。这个项目 使用创新的方法（ChannelRhopopsin辅助补丁），以促进针对性的有效性 在任何皮质深处记录特定细胞类型的体内记录，以促进我们对L4电路的理解。这 研究的重点是体感皮质的L4中的两个主要人群，即快速刺激性 白蛋白 - 表达篮细胞（PV INS）和表达生长抑素的INS（SST INS） 共同占L4 INS的80-90％。切片中的实验导致了以下假设 L4 SST INS是胆碱能影响的主要靶标，是调节活性的PV。 L4 PV INS 产生丘脑皮质输入的前馈抑制（FFI），从而控制了特征的选择性 L4 PNS。该应用将检验L4 SST INS调节PV内介导的PNS的假设， 并且由于SST细胞的胆碱能激活而在L4中产生的PNS的抑制作用 有助于ACH增强感觉检测的机制。调查抑制作用 假设，在AIM 1中，我们将研究L4 PV INS和PN在行为状态中的活性变化 SST通常会增加其活性以及操纵SST活性的影响。在AIM 2中，我们 将使用依赖胆碱能调节的感觉检测任务来研究L4 SST的作用 在触摸反应的活动中，以及SST INS的毒蕈碱激活对 感觉信号和行为表现的胆碱能增强。