title: Firing characteristics of deep dorsal horn neurons after acute spinal transection during administration of agonists for 5-HT1B/1D and NMDA receptors.
abstract: Spinal cord injury (SCI) results in a loss of serotonin (5-HT) to the spinal cord and a loss of inhibition to deep dorsal horn (DDH) neurons, which produces an exaggerated excitatory drive to motoneurons. The mechanism of this excitatory drive could involve the DDH neurons triggering long excitatory postsynaptic potentials in motoneurons, which may ultimately drive muscle spasms. Modifying the activity of DDH neurons with drugs such as NMDA or the 5-HT1B/1Dreceptor agonist zolmitriptan could have a large effect on motoneuron activity and, therefore, on muscle spasms. In this study, we characterize the firing properties of DDH neurons after acute spinal transection in adult mice during administration of zolmitriptan and NMDA, using the in vitro sacral cord preparation and extracellular electrophysiology. DDH neurons can be categorized into three major types with distinct evoked and spontaneous firing characteristics: burst (bursting), simple (single spiking), and tonic (spontaneously tonic firing) neurons. The burst neurons likely contribute to muscle spasm mechanisms because of their bursting behavior. Only the burst neurons show significant changes in their firing characteristics during zolmitriptan and NMDA administration. Zolmitriptan suppresses the burst neurons by reducing their evoked spikes, burst duration, and spontaneous firing rate. Conversely, NMDA facilitates them by enhancing their burst duration and spontaneous firing rate. These results suggest that zolmitriptan may exert its antispastic effect on the burst neurons via activation of 5-HT1B/1Dreceptors, whereas activation of NMDA receptors may facilitate the burst neurons in contributing to muscle spasm mechanisms following SCI.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Theeradej
authors.initials: T
authors.lastname: Thaweerattanasinp
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and Department of Physical Therapy and Human Movement Science, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Heckman
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Physical Therapy and Human Movement Science, Feinberg School of Medicine, Northwestern University, Chicago, Illinois v-tysseling@northwestern.edu.
authors.forename: Vicki M
authors.initials: VM
authors.lastname: Tysseling
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000494:pharmacology; D023303:Oxazolidinones / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D012447:Sacrum; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D046509:Tissue Culture Techniques; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; C470302:HTR1B protein, human; D023303:Oxazolidinones; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D016194:Receptors, N-Methyl-D-Aspartate; D058825:Serotonin 5-HT1 Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan; D016202:N-Methylaspartate
keywords: N-methyl-d-aspartate; deep dorsal horn neurons; serotonin; spinal cord injury