Trigeminal System Plasticity During Active Exploration

理解成人大脑可塑性的现象，无论是由脑损伤引发的 神经系统或通过学习新的技能，可能会提供一个基本的步骤 建立治疗神经疾病的新疗法。然而，该赛道 神经可塑性背后的机制大多仍不清楚。阐明这个问题的是 这是我们研究计划的中心重点。 在之前的资助期间，我们证明了皮质丘脑(CT)投影， 起源于大鼠初级躯体感觉皮质(S1)，对定义 大鼠腹后内侧核神经元感受野的时空结构 丘脑。我们的数据还显示，在外周去传入后，CT投影有助于 VPM神经元展示可塑性重组的能力。有趣的是，我们还发现， S1神经元和VPM神经元的触觉反应的幅度和持续时间随动物的 行为状态。综上所述，这些结果表明丘脑皮质内的感觉表征 循环(TCL)是一种塑料的、动态调制的构造，它是从异步 多个上行和下行兴奋性和抑制性传入的汇聚。最近，我们 我报告说，在活动期间，S1层之间的触觉信号处理是根本不同的 而不是被动触觉刺激。例如，与任务相关的激发频率调制可以在 触觉刺激。然而，到目前为止，解释这种巨大变化的电路机制 响应特性在很大程度上仍不清楚。在这里，我们建议检验这一假设，即在活动期间 触觉探测，多个皮质和皮质丘脑投射动态调制 S1神经元和VPM神经元的触觉反应的幅度和时程，以优化 触觉刺激的辨别。我们还提出了一种新的触觉辨别任务的学习 增强了这些“自上而下”的投影对TCL的影响。在这个项目中，我们建议重点关注 S1的两个主要输入：初级运动皮质(M1)和对侧S1。局灶性可逆性失活 M1或S1在动机辨别行为中对TCL反应有一定的贡献。 慢性记录方法将允许我们跟踪响应统计数据在过程中的变化 学习辨别任务。我们实验室首创的可移动电极技术使我们能够 将S1反应的层结构与解剖学上已知的投射联系起来。这些实验 提供了解神经系统的窗口，因为它动态地将广泛分布的神经信号集成到 执行一项不平凡的感觉-运动任务，并承诺对当前的感觉模型进行重大修改 主要基于对被动传递的刺激的电生理反应。

Understanding the phenomena of adult brain plasticity, triggered either by injury to the nervous system or by learning new skills, will likely provide a fundamental step towards establishing newtherapies for treating neurological disorders. However, the circuit mechanisms underlying neural plasticity remain mostly unknown. Elucidating this question is the central focus of our research program. During the previous funding period, we demonstrated that corticothalamic (CT) projections, originating in the rat primary somatosensory cortex (S1), significantly contribute to the definition of the spatiotemporal structure of the receptive fields of neurons in the ventroposterior medial nucleus (VPM) of the thalamus. Our data also revealed that, following a peripheral deafferentation, CT projections contribute to the ability of VPM neurons to exhibit plastic reorganization. Interestingly, we also found that both the magnitude and duration of tactile responses of S1 and VPM neurons change according to the animal's behavioral state. Together, these results indicate that sensory representations within the thalamocortical loop (TCL) are plastic, dynamically modulated constructs, which emerge from the asynchronous convergence of multiple ascending and descending excitatory and inhibitory afferents. Most recently, we have reported that tactile signal processing across S1 layers is fundamentally different during active versus passive tactile stimulation. For example, task-related modulation of firing rates can begin before tactile stimulation. To date, however, the circuit mechanisms to account for such gross changes in response properties remain largely unknown. Here we propose to test the hypothesis that, during active tactile exploration, multiple corticocortical and corticothalamic projections dynamically modulate the magnitude and duration of tactile responses of S1 and VPM neurons respectively, in order to optimize the discrimination of tactile stimuli. We also propose that learning of a new tactile discrimination task enhances the effects of these "top-down" projections on the TCL. In this project we propose to focus on two major inputs to S1: primary motor cortex (M1) and contralateral S1. Focal reversible inactivation of M1 or S1 would reveal their contribution to TCL responses during motivated discrimination behavior. Chronic recording methods would allow us to follow changes in response statistics over the course of learning the discrimination task. Moveable electrode technology, pioneered in our lab, enables us to correlate the layer structure of S1 responses with anatomically known projections. These experiments offer a window into the nervous system as it dynamically integrates widely distributed neural signals to carry out a non-trivial sensory-motor task, and promise significant revisions to current models of sensation based predominantly on electrophysiological responses to passively delivered stimuli.