Modulation of the intrinsic properties of motoneurons by serotonin

TY - JOUR

T1 - Modulation of the intrinsic properties of motoneurons by serotonin

AU - Perrier, Jean-François

AU - Rasmussen, Hanne Borger

AU - Christensen, Rasmus Kordt

AU - Petersen, Anders Victor

PY - 2013

Y1 - 2013

N2 - Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and its physiological consequences. The somato-dendritic compartments of motoneurons are densely innervated by serotonergic synaptic boutons and several receptors are expressed in the membrane of motoneurons including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C and 5-HT5A. The activation of serotonergic receptors induces a general increase of the excitability of motoneurons through the modulation of several classes of ion channels. 5-HT depolarizes motoneurons towards the threshold for action potentials by inhibiting leak conductances and promoting a hyperpolarization activated cationic current. At the same time, 5-HT increases the firing frequency by inhibiting the small Ca2+ activated K+ conductance (SK) responsible for the medium afterhyperpolarization (AHP) following action potentials. 5-HT also promotes persistent inward currents mediated by voltage sensitive Ca2+ and Na+ conductances, producing a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle spasms and spasticity and hence, impairment of stereotyped motor behaviors such as locomotion, ejaculation and micturition.

AB - Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and its physiological consequences. The somato-dendritic compartments of motoneurons are densely innervated by serotonergic synaptic boutons and several receptors are expressed in the membrane of motoneurons including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C and 5-HT5A. The activation of serotonergic receptors induces a general increase of the excitability of motoneurons through the modulation of several classes of ion channels. 5-HT depolarizes motoneurons towards the threshold for action potentials by inhibiting leak conductances and promoting a hyperpolarization activated cationic current. At the same time, 5-HT increases the firing frequency by inhibiting the small Ca2+ activated K+ conductance (SK) responsible for the medium afterhyperpolarization (AHP) following action potentials. 5-HT also promotes persistent inward currents mediated by voltage sensitive Ca2+ and Na+ conductances, producing a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle spasms and spasticity and hence, impairment of stereotyped motor behaviors such as locomotion, ejaculation and micturition.

KW - Action Potentials

KW - Animals

KW - Humans

KW - Motor Neurons

KW - Raphe Nuclei

KW - Receptors, Serotonin

KW - Serotonin

KW - Species Specificity

KW - Spinal Cord Injuries

U2 - 10.2174/13816128113199990341

DO - 10.2174/13816128113199990341

M3 - Journal article

C2 - 23360270

SN - 1381-6128

VL - 19

SP - 4371

EP - 4384

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

IS - 24

ER -