Grant: Project Grant

Serotonergic (5-HT) neurons projecting from the brain to the spinal cord are known to contribute to many key functions, such as respiratory, cardiac, sexual, motor function as well as the control of pain. The spinal neurons receiving information from serotonergic neurons with specific receptors are known to be important for contributing to recovery of locomotor function after spinal cord injury. The mechanisms by which serotonergic neurons control their spinal targets are in the focus of this project. By using cutting-edge methods to selectively activate or inhibit 5-HT neurons of the brainstem, we will identify which 5-HT neurons contribute the most to the control of locomotion. Transgenic rodent models allowing a chemogenetic or an optogenetic neural activation approach, we allow us to identify those brainstem neurons that can initiate locomotion and coordinate stepping. We will also identify the locomotor cells in the spinal cord that respond to 5-HT neuron stimulation. Moreover, developmental changes in the effects of 5-HT neurons will be examined at different ages in neonatal to adult animals in order to clarify the mechanisms by which serotonergic cells may control locomotion and pain processing. The proposed work is necessary to develop preclinical studies to facilitate recovery of walking after spinal cord injury. The long-term results will provide new pharmacological treatment options to be used for improving voluntary motor function and potential strategies for cell-replacement therapies involving serotonergic neuron transplants to expedite functional recovery after spinal cord injury.