Effects of spinal cord injury on intrinsic properties and serotonin sensitivity of locomotion coordinating interneurons

• Applicant: Dr. Andreas Husch
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 203473599

Spinal cord injury (SCI) causes two major problems for the restoration of locomotor function. First, it eliminates rapid synaptic and slow modulatory inputs from the brain to the spinal locomotor central pattern generator (CPG) networks that are essential for normal activation of locomotion. Second, the isolated spinal cord undergoes slow denervation-induced changes, including alterations in synaptic strength and intrinsic properties of spinal neurons. This could affect the proper function of the CPG. Most current research on recovery from SCI focuses on the first problem. I hypothesize that the second problem is just as serious: if the CPG networks become dysfunctional over time due to the loss of descending synaptic and modulatory inputs, restoration of inputs may come too late to restore function. Therefore I will study the effect of SCI on properties of locomotor controlling interneurons. With my preliminary work, I have solved the longstanding problem in the field, to record from adult, behaviorally mature mouse spinal interneurons, by a combination of new surgical techniques and perforated patch recordings. For the first time, I can study the intrinsic properties and serotonergic neuromodulation of identified interneurons in adult mouse spinal cords. With this essential baseline I will examine the changes in intrinsic properties of identified interneurons after SCI. I will then address the possible physiological mechanisms for these changes and whether replacement therapy with serotonin agonists after spinal cord injury prevents the plastic changes. I will work with transgenic mice that express fluorescent proteins in spinal V2a interneurons. My preliminary data confirm the feasibility of the project and indicate that there are substantial changes in the properties of spinal interneurons after SCI. It is likely that changes in the properties of locomotion coordinating interneurons impair recovery of locomotor function after SCI.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Ronald M. Harris-Warrick