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 reinitiate motor learning in the brain and promote plasticity in the motor cortex to restore lost movements (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 from our lab has identified an activity-dependent transcription factor, NPAS4, that is specifically expressed in an inhibitory neuron subtype in the motor cortex during motor learning. Most importantly, these inhibitory neurons reduce their inhibition to promote local circuit reorganization during movement acquisition.
However, it still remains unclear whether and how neuronal circuits in M1 are reorganized during the acquisition of different motor movements. Here, we propose a series of experiments employing live twophoton imaging, combined with various genetic tools, in awake and behaving mice to examine the functional role of learning-related neuronal ensembles during the acquisition of different motor movements. By deciphering the basic mechanisms underlying motor movement acquisition in health brains, our work has immense potential to promote plasticity in dysfunctional circuits altered in diseased brains and to aid the development of novel therapeutic targets for motor-related brain diseases.
