Serotonergic modulation of intracellular calcium dynamics in neonatal hypoglossal motoneurons from mouse

Abstract (1) Serotonin (5HT)-mediated calcium signaling was investigated in hypoglossal motoneurons (HGMs) in brain stem slices of neonatal mice. Electrical activity and associated calcium signaling were studied by simultaneous patch clamp recordings and high resolution calcium imaging. (2) Bath application of 5HT (5–50 μM) depolarized membrane potential of HGMs and generated action potential discharges that were accompanied by elevations in intracellular calcium concentrations ([Ca 2+ ] i ) in the soma and dendrites. Current-evoked bursts of action potentials were more intense in the presence of 5HT; however, the corresponding calcium signals were reduced. (3) The 5HT 2 receptor agonist α-Methyl-5HT (25, 50 μM) had effects on membrane potential, discharge properties and [Ca] i that were identical to those observed for 5HT, whereas the 5HT 3 receptor agonist 1-(m-chlorophenyl) biguanide (50 μM) had no effect on membrane properties or intracellular calcium levels. (4) 8-OHDPAT (25, 50 μM), a 5HT 1A receptor agonist, was without effect on steady-state membrane potential or basal [Ca] i . Similar to 5HT and α-Methyl-5HT, 8-OHDPAT depressed stimulus-evoked calcium transients in current and voltage clamp mode. (5) Our results suggest that calcium profiles in hypoglossal motoneurons are differentially regulated by 5HT 1A and 5HT 2 receptors. Activation of 5HT 1A receptors primarily reduced voltage-activated Ca 2+ signals without a significant impact on basal [Ca] i . In contrast, activation of 5HT 2 receptors initiated a net inward current followed by membrane depolarization, where the resulting pattern of action potential discharges represents the essential determinant of global elevations in [Ca 2+ ] i . Taken together, our results therefore identify 5HT-dependent signal pathways as a versatile tool to modulate hypoglossal motoneuron excitability under various physiological and pathophysiological conditions.