Cortical Control of Movement

描述（由申请人提供）：微须运动——老鼠在探索环境时进行的有节奏的微须运动——正在成为一种非常有前途的模型，用于研究控制自主运动的机制。由于缺乏对这一重要运动行为负责的通路和机制的数据，该模型的开发受到限制。在目前的资助期内，我们有了令人兴奋的发现，血清素能运动前神经元是产生面部运动神经元节律性放电的必要条件和充分条件。因此，这些血清素能神经元是中枢模式发生器（CPG）的关键组成部分。我们还发现，这种5 -羟色胺能CPG接收来自运动皮层（wMCx）的须状表征的密集输入。最后，我们证明，与普遍的教条相反，wMCx病变显著影响搅拌运动学和节律性。我们的中心假设是基于这些趋同的发现。研究表明，wMCx调节血清素能CPG的活性，CPG调节探索性搅拌的频率，这是一种对感觉运动整合和辨别能力至关重要的功能。从这个中心假设出发，我们制定并测试了三个新的假设，旨在全面理解这一重要运动行为背后的神经机制：

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.