Serotonin, Dopamine and Noradrenaline Adjust Actions of Myelinated Afferents via Modulation of Presynaptic Inhibition in the Mouse Spinal Cord

• Type of Material: Article
• Authors: David L. Garcia-Ramirez, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional; Jorge R. Calvo, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional; Shawn Hochman, Emory University; Jorge N. Quevedo, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional
• Language: English
• Date: 2014-02-28
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Garcı´a-Ramı´rez et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0089999
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 9
• Issue: 2
• Start Page: e89999
• End Page: e89999
• Grant/Funding Information: This work was supported by the following grants: CONACyT 59873 (J.Q), México (http://www.conacyt.gob.mx) and National Institutes of Health (NIH) NS-065949 (S.H), USA (http://www.nih.gov).
• Keywords: NEONATE RAT; MULTIDISCIPLINARY SCIENCES; Science & Technology; SUBSTANTIA-GELATINOSA NEURONS; DORSAL-HORN NEURONS; NOCICEPTIVE RESPONSES; IN-VITRO; RAPHE MAGNUS; II MUSCLE AFFERENTS; SYNAPTIC-TRANSMISSION; Multidisciplinary Sciences; Science & Technology - Other Topics; RECEPTOR; ROOT POTENTIALS
• Research Categories: Biology, Physiology; Biology, Neuroscience; Biology, General

Abstract

Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD). PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT), dopamine (DA) and noradrenaline (NA) on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs) or intracellular excitatory postsynaptic currents (EPSCs). The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs) recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75%) but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 mM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferentevoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic transmission in the dorsal horn are broadly reduced by descending monoamine transmitters. These actions likely integrate with modulatory actions elsewhere to reconfigure spinal circuits during motor behaviors.