A unique inhibitory interneuron that regulates sensory coding in neocortex

项目总结 这个项目的目标是研究大脑皮层最深层如何调节感官知觉。 通过一种独特类型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 在去新大脑皮层的路上。第六层(L6)皮质丘脑(CT)神经元将大量反馈投射发送到 丘脑，它们也发送上行侧支，能够强烈地调节皮质本身。近期 间接证据表明，这种调节可能是通过一种不同类型的快速尖峰(FS)--小白蛋白--来实现的。 表达驻留在L6上部的抑制性中间神经元，并将轴突独特地发送到上层，在那里 它们可能具有很强的跨层抑制作用。因为来自丘脑的主要感觉通路 在这些区域最显著地进入大脑皮层，这种连接暗示着对感觉的强烈调节作用。 对知觉加工的输入和影响。 FS中间神经元与伽马振荡密切相关，并与认知缺陷有关。 (Carlen等人，2012年；Korotkova等人，2010年)和精神分裂症(Lewis等人，2012年)。L6-CT细胞也被 与这些疾病有牵连。FS细胞在伽马节律中的作用提示L6 CT→FS连接 可能通过在感觉输入层施加同步性来调节大脑皮层，从而影响感知处理。这个 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实现的 L6-CT回路，以及这条抑制通路如何参与对刺激的感知。 第一个目标是确定CT细胞可以调节皮层内感觉处理的解剖回路。 具体地说，我将系统地确定L6-FS中间神经元连接的频率和强度 已知的神经元类型横跨皮质柱层。我将检验上L6-FS细胞形成的假设 与上覆皮质柱中特定神经元亚群的强联系，如锥体细胞 L2/3、4和5以及L4-FS信元，以及它们的外部连接规则是否进一步区分此类 来自其他FS细胞。目标2将测试不同的中间神经元组是否可以协调 上面的柱子。具体地说，这将检验上L6的跨层流FS细胞包含唯一的 支持快速振荡节律协调的内在生理特性，并调节 在体外CT诱发的伽马试验中观察到LFP的网络节律活动。目标3将测试假定的 上L6-FS细胞在检测清醒行为动物的任务表现和振荡活动中的作用。 这项拟议的调查将阐明一种独特电路的重要功能，并在这样做的过程中提供 申请人在几项关键的体外和体内技术方面进行了重要的培训。由提供的宝贵培训 两个具有互补专业知识的共同赞助者将对体外电路解剖和演示至关重要 这些回路在活体内的行为相关性。

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.