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Identifying the cell-type specific transcriptional program by Npas4 in motor learning

Principal Investigator:
  • Simon Chen, University of Ottawa

Project Overview

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 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 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 propose a series of experiments employing live two-photon imaging, combined with various genetic tools, in awake and behaving mice to elucidate the role of Npas4 in motor learning. 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.