Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors
Katherine C Murray, Aya Nakae, Marilee J Stephens, Michelle Rank, Jessica D'Amico, Philip J Harvey, Xiaole Li, R Luke W Harris, Edward W Ballou, Roberta Anelli, Charles J Heckman, Takashi Mashimo, Romana Vavrek, Leo Sanelli, Monica A Gorassini, David J Bennett, Karim Fouad
NATURE MEDICINE | NATURE PUBLISHING GROUP | Published : 2010
Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons r..View full abstract
Awarded by US National Institutes of Health
Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Thanks to F. Geddes, T. Tanaka, K. Miyake, G. Van Patten, J. Nevett-Duchcherer, G. Funk, M. Finlay and L. Hahn for assistance. This research was supported by the Alberta Heritage Foundation, Canadian Institutes of Health Research and the US National Institutes of Health (NS47567 and NS48170).