Cortical Control of Movement

描述(由申请者提供)：扭动--老鼠在探索环境时进行的有节奏的胡须运动--正在成为研究控制自愿运动的机制的一个非常有前途的模型。由于缺乏有关这一重要运动行为的途径和机制的数据，这一模型的开发一直受到限制。在当前的资助期间，我们有了一个令人兴奋的发现，即5-羟色胺能前运动神经元是控制扭动的面部运动神经元产生节律性放电的必要条件和充分条件。因此，这些5-羟色胺能神经元是中枢模式发生器(CPG)的关键组成部分，用于有节奏的搅拌。我们还发现，这种5-羟色胺能CPG从运动皮质的胡须代表(WMCx)接受密集的输入。最后，我们证明--与流行的教条相反--wMCx的损伤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。它指出，wMCx调节5-羟色胺能CPG的活动，该活动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。根据这一中心假设，我们提出并测试了三个新的假设，旨在全面了解这一重要运动行为背后的神经机制： 假设一：控制甩动的面部运动神经元(甩动运动神经元)由相互的电突触同步。 假设二：CPG释放的5-羟色胺动态调节搅拌频率。 假设III：wMCx通过作用于5-羟色胺能CPG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.