title: Locomotor networks are targets of modulation by sensory transient receptor potential vanilloid 1 and transient receptor potential melastatin 8 channels.
abstract: It is well recognized that proprioceptive afferent inputs can control the timing and pattern of locomotion. C and Adelta afferents can also affect locomotion but an unresolved issue is the identity of the subsets of these afferents that encode defined modalities. Over the last decade, the transient receptor potential (TRP) ion channels have emerged as a family of non-selective cation conductances that can label specific subsets of afferents. We focus on a class of TRPs known as ThermoTRPs which are well known to be sensor receptors that transduce changes in heat and cold. ThermoTRPs are known to help encode somatosensation and painful stimuli, and receptors have been found on C and Adelta afferents with central projections onto dorsal horn laminae. Here we show, using in vitro neonatal mouse spinal cord preparations, that activation of both spinal and peripheral transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) afferent terminals modulates central pattern generators (CPGs). Capsaicin or menthol and cooling modulated both sacrocaudal afferent (SCA) evoked and monoaminergic drug-induced rhythmic locomotor-like activity in spinal cords from wild type but not TRPV1-null (trpv1(-/-)) or TRPM8-null (trpm8(-/-)) mice, respectively. Capsaicin induced an initial increase in excitability of the lumbar motor networks, while menthol or cooling caused a decrease in excitability. Capsaicin and menthol actions on CPGs involved excitatory and inhibitory glutamatergic mechanisms, respectively. These results for the first time show that dedicated pathways of somatosensation and pain identified by TRPV1 or TRPM8 can target spinal locomotor CPGs.
authors.affiliation: Hotchkiss Brain Institute, 3330 Hospital Drive Northwest, Calgary, AB, T2N 4N1 Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mandadi
authors.forename: S T
authors.initials: ST
authors.lastname: Nakanishi
authors.forename: Y
authors.initials: Y
authors.lastname: Takashima
authors.forename: A
authors.initials: A
authors.lastname: Dhaka
authors.forename: A
authors.initials: A
authors.lastname: Patapoutian
authors.forename: D D
authors.initials: DD
authors.lastname: McKemy
authors.forename: P J
authors.initials: PJ
authors.lastname: Whelan
mesh_terms: D000344:Afferent Pathways; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology; D003080:Cold Temperature; D006614:Hindlimb / Q000294:innervation; D066298:In Vitro Techniques; D008610:Menthol / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D018689:Sensory System Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D050053:TRPM Cation Channels / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000502:physiology*
chemical_list: D018689:Sensory System Agents; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D008610:Menthol; D002211:Capsaicin