Grant: Project Grant

The primary motor cortex in the brain is responsible for voluntary movement. It has also been proposed to be one of the sites for motor memory formation and storage. Therefore, when the motor cortex is damaged following a stroke, we lose the ability to execute movements that were formerly part of normal daily life. One hypothesis to achieve true recovery is to re-initiate motor learning in the brain and establish new representation to replace the destroyed ones (Murphy and Corbett, 2009). Hence, a determination of the basic molecular mechanisms underlying motor learning will enhance our understanding of post-traumatic rehabilitation in brain injury and disease. Previous work has demonstrated the importance of local inhibitory circuits in the motor cortex in regulating the acquisition of new motor skills. Our lab has recently identified an activity-dependent transcription factor, Npas4, that is specific expressed in an inhibitory neuron subtype in the motor cortex during motor learning. Here, we are proposing a series of experiments employing in vivo two-photon imaging combined with head-fixed pellet-reaching motor skill learning task to elucidate the role of Npas4 in learning-driven inhibitory neural circuit modifications during motor learning in awake and behaving mice. By deciphering the basic mechanisms underlying motor movement acquisition in normal healthy brains, our work has immense potential to promote plastic changes in dysfunctional circuits altered by stroke and aid in the development of novel therapeutic targets for stroke recovery and other brain injuries impairing motor function