title: Serotonin 1A receptors alter expression of movement representations.
abstract: Serotonin has a myriad of central functions involving mood, appetite, sleep, and memory and while its release within the spinal cord is particularly important for generating movement, the corresponding role on cortical movement representations (motor maps) is unknown. Using adult rats we determined that pharmacological depletion of serotonin (5-HT) via intracerebroventricular administration of 5,7 dihydroxytryptamine resulted in altered movements of the forelimb in a skilled reaching task as well as higher movement thresholds and smaller maps derived using high-resolution intracortical microstimulation (ICMS). We ruled out the possibility that reduced spinal cord excitability could account for the serotonin depletion-induced changes as we observed an enhanced Hoffman reflex (H-reflex), indicating a hyperexcitable spinal cord. Motor maps derived in 5-HT1A receptor knock-out mice also showed higher movement thresholds and smaller maps compared with wild-type controls. Direct cortical application of the 5-HT1A/7 agonist 8-OH-DPAT lowered movement thresholds in vivo and increased map size in 5-HT-depleted rats. In rats, electrical stimulation of the dorsal raphe lowered movement thresholds and this effect could be blocked by direct cortical application of the 5-HT1A antagonist WAY-100135, indicating that serotonin is primarily acting through the 5-HT1A receptor. Next we developed a novel in vitro ICMS preparation that allowed us to track layer V pyramidal cell excitability. Bath application of WAY-100135 raised the ICMS current intensity to induce action potential firing whereas the agonist 8-OH-DPAT had the opposite effect. Together our results demonstrate that serotonin, acting through 5-HT1A receptors, plays an excitatory role in forelimb motor map expression.
authors.affiliation: Hotchkiss Brain Institute, Department of Neuroscience, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Scullion
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Boychuk
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Yamakawa
authors.forename: Justin T G
authors.initials: JT
authors.lastname: Rodych
authors.forename: Stan T
authors.initials: ST
authors.lastname: Nakanishi
authors.forename: Angela
authors.initials: A
authors.lastname: Seto
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Smith
authors.forename: Ryan W
authors.initials: RW
authors.lastname: McCarthy
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Whelan
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Pittman
authors.forename: G Campbell
authors.initials: GC
authors.lastname: Teskey
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D002851:Chromatography, High Pressure Liquid; D005552:Forelimb / Q000187:drug effects / Q000502:physiology; D006181:H-Reflex / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009068:Movement / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000172:deficiency / Q000378:metabolism*; D012701:Serotonin / Q000172:deficiency; D018490:Serotonin Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D010879:Piperazines; D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014365:Tryptophan Hydroxylase