Trigeminal System Plasticity During Active Exploration

了解成人大脑可塑性的现象，无论是由损伤引发的， 神经系统或通过学习新技能，可能会提供一个基本的步骤， to establish建立newtherapies疗法for treating治疗neurological神经disorders紊乱.然而，电路 神经可塑性的潜在机制仍然是未知的。解释这个问题的是 我们的研究项目的核心。 在上一个资助期间，我们证明了皮质丘脑（CT）预测， 起源于大鼠初级躯体感觉皮层（S1），显著有助于定义 腹后内侧核（VPM）神经元感受野的时空结构 丘脑我们的数据还显示，在外周传入神经阻滞后，CT投影有助于 VPM神经元表现出可塑性重组的能力。有趣的是，我们还发现， S1和VPM神经元触觉反应的幅度和持续时间根据动物的 行为状态总之，这些结果表明，丘脑皮质内的感觉表征 循环（TCL）是可塑的，动态调制的结构，从异步 多个上行和下行兴奋性和抑制性传入的会聚。最近，我们 据报道，在活动过程中，S1层的触觉信号处理是根本不同的。 与被动触觉刺激相比。例如，任务相关的激发率调制可以在任务完成之前开始。 触觉刺激然而，到目前为止，电路机制，以占这种总的变化， 响应特性在很大程度上仍然未知。在这里，我们建议测试的假设，在积极的 触觉探索，多皮质和皮质丘脑的预测动态调节 S1和VPM神经元的触觉反应的幅度和持续时间，以优化 对触觉刺激的辨别。我们还提出，学习一种新的触觉辨别任务， 增强了这些“自上而下”的预测对TCL的影响。在本项目中，我们建议将重点放在 S1的两个主要输入：初级运动皮层（M1）和对侧S1。局灶性可逆失活 M1和S1在动机性歧视行为中对TCL反应的贡献较大。 长期记录方法将使我们能够跟踪反应统计数据在整个过程中的变化， 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影相关联。这些实验 为神经系统提供了一个窗口，因为它动态地整合了广泛分布的神经信号， 执行一项重要的感觉运动任务，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.