A unique inhibitory interneuron that regulates sensory coding in neocortex

调节新皮质感觉编码的独特抑制性中间神经元

• 批准号: 10272423
• 负责人: Frank Scott Susi
• 金额: $ 4.6万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10272423
• 关键词: Anatomy; Animals; Axon; Back; Behavioral; Brain; Cells; Cerebral cortex; Code; Cognitive deficits; Communication; Cortical Column; Detection; Disease; Dissection; Esthesia; Feedback; Frequencies; Generations; Goals; In Vitro; Interneurons; Investigation; Leg; Light; Mediating; Neocortex; Neurons; Output; Parvalbumins; Pathway interactions; Pattern; Perception; Performance; Periodicity; Phenotype; Physiological; Play; Population; Positioning Attribute; Probability; Process; Property; Pyramidal Cells; Ramp; Role; Route; Schizophrenia; Sensory; Signal Transduction; Slice; Stereotyping; Stimulus; Subgroup; Suggestion; Synapses; Synaptic Potentials; Task Performances; Techniques; Testing; Thalamic structure; Training; Whole-Cell Recordings; awake; barrel cortex; cell type; deviant; experimental study; in vivo; information processing; neural circuit; object perception; optogenetics; prospective; recruit; sensory input; sensory stimulus; somatosensory

PROJECT SUMMARY The goal of this project is to investigate how the deepest layer in the neocortex can modulate sensory perception through a unique type of inhibitory interneuron. Almost all sensory information proceeds through the thalamus en route to the neocortex. Layer 6 (L6) corticothalamic (CT) neurons send massive feedback projections to the thalamus, and they also send ascending collaterals capable of strongly modulating the cortex itself. Recent indirect evidence suggests this modulation may occur through a distinct type of fast-spiking (FS), parvalbumin- expressing inhibitory interneuron that resides in upper L6 and uniquely sends axons into the upper layers where they presumably impart strong translaminar inhibition. Because the primary sensory pathway from the thalamus enters cortex most prominently in these zones, this wiring is suggestive of strong modulatory effects on sensory inputs and influence on perceptual processing. FS interneurons are critically involved in gamma oscillations and have been implicated in cognitive deficits (Carlen et al., 2012; Korotkova et al., 2010) and schizophrenia (Lewis et al., 2012). L6-CT cells have also been implicated in these disorders. The role of FS cells in gamma rhythms suggests that the L6 CT→FS connectivity may modulate the cortex by imposing synchrony on sensory input layers to influence perceptual processing. The central goal of this proposal is to determine how modulation of sensory information is implemented by intracortical L6-CT circuits, and how this inhibitory pathway participates in the perception of stimuli. Aim 1 is to determine the anatomical circuits by which CT cells can modulate sensory processing within cortex. Specifically, I will systematically determine the frequency and strength by which L6-FS interneurons connect to known neuron types across the layers of a cortical column. I will test the hypothesis that upper L6-FS cells form strong connections with specific neuronal subsets in the overlying cortical column, such as pyramidal cells in L2/3, 4, and 5, as well as L4-FS cells, and whether their extrinsic connectivity rules further distinguish this class from other FS cells. Aim 2 will test whether distinct groups of interneurons can coordinate rhythms in the overlying column. Specifically, this will test the hypotheses that translaminar FS cells of upper L6 contain unique intrinsic physiological properties that support the coordination of fast oscillatory rhythms, and mediates the network rhythmic activity observed in LFPs during CT-evoked gamma in vitro. Aim 3 will test the role of putative upper L6-FS cells in detection task performance and oscillatory activity in the awake behaving animal. This proposed investigation will illuminate important functions of a unique circuit, and in doing so will provide the applicant significant training in several critical in vitro and in vivo techniques. The valuable training provided by two Co-Sponsors with complementary expertise will be critical for in vitro circuit dissection and for demonstrating the behavioral relevance of those circuits in vivo.

项目摘要 这个项目的目标是研究新皮层的最深层是如何调节感官知觉的 通过一种独特的抑制性中间神经元。几乎所有的感觉信息都是通过丘脑传递的 在通往大脑皮层的路上第6层（L 6）皮质丘脑（CT）神经元发送大量的反馈投射到 丘脑，他们也发送上行侧支能够强烈调节皮质本身。最近 间接证据表明，这种调节可能通过一种独特的快速尖峰（FS），小清蛋白发生， 表达抑制性中间神经元，其位于L 6上部，并且唯一地将轴突发送到上层， 它们可能赋予强的跨层抑制作用。因为从丘脑开始的初级感觉通路 在这些区域中最显著地进入皮层，这种布线暗示了对感觉的强烈调节作用。 输入和对感知处理的影响。 FS中间神经元与γ振荡密切相关，并与认知缺陷有关 （Carlen等人，2012; Korotkova等人，2010）和精神分裂症（刘易斯等人，2012年）。L 6-CT细胞也被 与这些疾病有关。FS细胞在γ节律中的作用表明，L 6 CT→FS连接 可能通过在感觉输入层上施加同步来调节皮层，以影响感知处理。的 这项建议的中心目标是确定感觉信息的调制是如何通过皮层内的 L 6-CT电路，以及这种抑制通路如何参与刺激的感知。 目的1是确定CT细胞调节皮层感觉加工的解剖回路。 具体地说，我将系统地确定L 6-FS中间神经元连接的频率和强度。 已知的神经元类型在皮层柱的各层上。我将检验L 6-FS上部细胞 与上覆皮质柱中的特定神经元亚群的强连接，例如大脑中的锥体细胞。 L2/3、4和5以及L4-FS细胞，以及它们的外部连接规则是否进一步区分这类细胞 其他FS细胞。Aim 2将测试不同的中间神经元组是否可以协调大脑中的节律。 上覆柱。具体而言，这将检验上L 6的跨层FS细胞含有独特的 支持快速振荡节律协调的内在生理特性，并介导 在体外CT诱发的伽马射线期间在LFP中观察到的网络节律活动。目标3将测试假定的 上L 6-FS细胞的检测任务的性能和振荡活动的清醒行为的动物。 这项拟议的调查将阐明一个独特的电路的重要功能，并在这样做将提供 申请人在几种关键的体外和体内技术方面接受过重要培训。提供的宝贵培训 两个具有互补专业知识的共同申办者对于体外回路解剖和证明 这些回路在体内的行为相关性。