Synaptic Release of Serotonin Induced by Stimulation of the Raphe Nucleus Promotes Plateau Potentials in Spinal Motoneurons of the Adult Turtle

Abstract

Serotonin (5-HT

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

“…1A) (22), in the presence of blockers for fast glutamate, GABA, and glycine synaptic transmission (SI Materials and Methods). In agreement with previous studies (26,31,33), we found that a brief stimulation of the DLF (1 s at 10-40 Hz) increased the excitability of MNs because the number of APs generated by depolarizing current pulses was significantly increased ( Fig. 1B; from 1.00 to 1.73 ± 0.15; Wilcoxon test; n = 15 pairs).…”

“…Most in vitro studies performed with bath applied drugs report that 5-HT promotes the excitability of MNs by modulating resting conductances (23), the medium after hyperpolarization following APs (25) or persistent inward currents mediated by Ca 2+ (28,31,33) or Na + channels (27). Most of these modulations are caused by the activation of 5-HT 2 receptors located in the somatodendritic compartments.…”

“…1B; from 1.00 to 1.73 ± 0.15; Wilcoxon test; n = 15 pairs). This effect is caused by the activation of somatodendritic 5-HT 2 receptors, which facilitate a persistent inward current (PIC) mediated by L-type Ca 2+ channels (31,33). Because the rate of discharge of raphe neurons is correlated with motor activity (19), we tested the effect of a prolonged DLF stimulation, mimicking the release of 5-HT occurring during long efforts.…”

“…Finally, spinal MNs are densely innervated by serotonergic synaptic terminals (21,22). These results are nonetheless puzzling because of studies that demonstrate that 5-HT promotes the activity of MNs by inhibiting leak conductances (23,24), Ca 2+ -activated K + conductances (25), and by facilitating persistent inward currents (26)(27)(28)(29)(30)(31)(32). How can 5-HT boost the activity of MNs and, thereby, muscle contraction and at the same time induce central fatigue?…”

Molecular and Electrical Abnormalities in the Mouse Model of Amyotrophic Lateral Sclerosis

“…The neuroinflammation response is a promising approach (Philips and Robberecht, 2011); another could be to manipulate neuromodulatory input to the spinal cord. Serotonin (5HT) and norepinephrine (NE) have potent effects on motoneurons, including increasing PIC amplitude, decreasing input conductance, hyperpolarizing spike threshold, and depolarizing resting potential (Hounsgaard and Kiehn, 1989, Lee and Heckman, 1999, Powers and Binder, 2001, Alaburda et al, 2002, Hultborn et al, 2004, Perrier and Delgado-Lezama, 2005, Heckman et al, 2008. Furthermore, neuromodulators are constantly scaling the level of activation of motoneurons as needed (Heckman et al, 2004).…”