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

• Final Report Year: 2014

Final Report Abstract

Denervation induced changes in the locomotor controlling neuronal networks of the spinal cord might impair locomotor recovery after spinal cord injury. Because of longstanding difficulties in recording spinal interneurons from adult mice, the impact of spinal cord injury on spinal interneurons has not been studied in the past. During my fellowship, I have established a protocol to record from spinal interneurons in adult mice of any age. This allows investigation of changes in mature neuronal properties in disease states or after spinal cord injury. I analyzed the effects of complete spinal cord lesions on the intrinsic electrophysiological properties, excitability and neuromodulatory responses to serotonin (5-HT) in mouse lumbar V2a spinal interneurons, which help regulate left-right alternation during locomotion. Four weeks after spinal cord injury, V2a interneurons showed almost no changes in baseline excitability or action potential properties; the only parameter that changed was a reduced input resistance. However, V2a interneurons became 100-1000 fold more sensitive to 5-HT. Immunocytochemical analysis showed that spinal cord injury caused a coordinated loss of serotonergic fibers and 5-HT transporters as well as an increase in 5-HT2C receptor cluster number and intensity, suggesting that several plastic changes cooperate in increasing 5-HT sensitivity. These results highlight the importance of understanding the plastic changes on the cellular level when considering therapies targeted at functional recovery.

Publications

• (2011) Differences in serotonin responsiveness in mouse spinal V2a interneurons using perforated patch and whole cell recording techniques. Neuroscience Meeting Planner. Washington, DC. Society for Neuroscience, Online
  Dietz S, Husch A and Harris-Warrick RM
  
• (2011) Long-duration perforated patch recordings from spinal interneurons of adult mice. Journal of Neurophysiology 106(5):2783-9
  Husch A, Cramer N, Harris-Warrick RM
  
• 2011) Influence of spinal cord injury induced serotonin transporter reduction on serotonin responsiveness in V2a interneurons. Neuroscience Meeting Planner. Washington, DC. Society for Neuroscience, Online
  Husch A and Harris-Warrick RM
  
• (2012) A comparison of serotonin neuromodulation of mouse spinal V2a interneurons using perforated patch and whole cell recording techniques. Frontiers in Cellular Neuroscience 6:39
  Dietz SB, Husch A, Harris-Warrick RM
  
• (2012) From nonmoving neonates to locomoting adults: spinal V2a interneurons change excitability and 5-HT modulation with maturation. Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, Online
  Husch A, Dietz S and Harris-Warrick RM
  
• (2012) Spinal cord injury induces serotonin supersensitivity without increasing intrinsic excitability of mouse V2a interneurons. Journal of Neuroscience 32(38):13145-13154
  Husch A, Van Patten GN, Hong DN, Scaperotti MM, Cramer N, Harris-Warrick RM
  
• (2013) Spinal cord injury increases baseline firing and serotonin sensitivity but not bistability in mouse spinal motoneurons. Motor Systems Symposium, Salk institute, La Jolla, CA
  Husch A, Johnson BJ and Harris-Warrick RM