Cortical Control of Movement

描述（由申请人提供）：Whisking-大鼠在探索其环境时进行的有节奏的胡须运动-正在成为一种非常有前途的模型，用于研究控制自愿运动的机制。由于缺乏有关这一重要运动行为的途径和机制的数据，这一模型的开发受到限制。在目前的资助期间，我们取得了令人兴奋的发现，即多巴胺能前运动神经元是必要的，也足以在控制搅拌的面部运动神经元中产生有节奏的放电。因此，这些多巴胺能神经元是用于节律性搅拌的中央模式发生器（CPG）的关键组成部分。我们还表明，这是一个神经元能的CPG接收密集的输入，从胡须代表的运动皮层（wMCx）。最后，我们证明了-与流行的教条相反-wMCx的病变显着影响搅拌运动学和节奏。我们的中心假设是基于这些趋同的发现。它指出，wMCx调节神经元能CPG的活性，该CPG调节探索性搅拌的频率，这是感觉运动整合和辨别能力的关键功能。从这个中心假设出发，我们提出并检验了三个新的假设，旨在全面理解这一重要运动行为背后的神经机制： 假设一：控制拂动的面部运动神经元（拂动运动神经元）通过相互电突触同步。 假设二：从CPG释放的血清素动态调节搅拌频率。 假设III：wMCx通过其对能神经递质的CPG的作用来调节搅拌频率。

DESCRIPTION (provided by applicant): Whisking--the rhythmic whisker movements that rats perform while exploring their environment--is emerging as an exceptionally promising model for investigating mechanisms that control of voluntary movements. Exploitation of this model has been limited by lack of data on the pathways and mechanisms responsible for this important motor behavior. In the current funding period we made the exciting discovery that serotonergic pre-motoneurons are both necessary and sufficient to generate rhythmic firing in the facial motoneurons that control whisking. Thus, these serotonergic neurons are a critical component of a central pattern generator (CPG) for rhythmic whisking. We also showed that this serotonergic CPG receives dense inputs from the whisker representation of the motor cortex (wMCx). Finally, we demonstrated that--contrary to prevailing dogma--lesions of wMCx significantly affect whisking kinematics and rhythmicity. Our central hypothesis is based on these convergent findings. It states that wMCx modulates the activity of the serotonergic CPG that regulates the frequency of exploratory whisking, a function critical for sensorimotor integration and discrimination abilities. From this central hypothesis we formulate and test three novel hypotheses directed at a complete understanding of the neural mechanisms underlying this important motor behavior: Hypothesis I: Facial motoneurons that control whisking (whisking motoneurons) are synchronized by reciprocal electrical synapses. Hypothesis II: Serotonin released from the CPG dynamically regulates whisking frequency. Hypothesis III: wMCx modulates whisking frequency by its action on the serotonergic CPG.