Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord

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 complex...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e89999-e89999
Main Authors: García-Ramírez, David L, Calvo, Jorge R, Hochman, Shawn, Quevedo, Jorge N
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Back propagation
Biology
Brain research
Depolarization
Dopamine
Dopamine - pharmacology
Dorsal horn
Dorsal roots
Electric Stimulation
Evaluation
Evoked Potentials - drug effects
Evoked Potentials - physiology
Excitability
Excitatory postsynaptic potentials
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Experiments
Fibers
Ganglia, Spinal - cytology
Ganglia, Spinal - drug effects
Ganglia, Spinal - physiology
Hindlimb
Information processing
Inhibition
Laboratory animals
Mental depression
Metabotropic receptors
Mice
Modulation
Monoamines
Muscles
Myelin Sheath - drug effects
Myelin Sheath - physiology
Neonates
Nervous system
Neural Inhibition - drug effects
Neural Inhibition - physiology
Neurons, Afferent - cytology
Neurons, Afferent - drug effects
Neurons, Afferent - physiology
Neurosciences
Neurotransmission
Neurotransmitter release
Noradrenaline
Norepinephrine
Norepinephrine - pharmacology
Phenols (Class of compounds)
Presynapse
Receptor mechanisms
Rodents
Sensory integration
Sensory neurons
Serotonin
Serotonin - pharmacology
Spinal cord
Spinal Cord - cytology
Spinal Cord - drug effects
Spinal Cord - physiology
Synapses - drug effects
Synapses - physiology
Transmitters
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Summary: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 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0089999