Modulation of hypoglossal motoneuron excitability by intracellular signal transduction cascades.

Motoneuronal excitability is highly modulated by various inputs; however, comparatively little is known about postsynaptic signal transduction cascades that affect motoneuron excitability. In this review, we discuss the role of intracellular signaling cascades in the modulation of respiratory motoneuronal excitability. In particular, protein kinases and phosphatases dynamically and constitutively modulate respiratory-modulated inputs to XII motoneurons: (i) activation of protein kinase A (PKA) potentiates both excitatory and inhibitory drive currents; (ii) protein kinase G (PKG) depresses excitatory currents, and (iii) inhibition of protein phosphatases potentiates excitatory drive currents. We also describe a novel form of persistent plasticity (in vitro long-term facilitation; ivLTF) of motoneuronal output. ivLTF is induced by episodic activation of 5-HT(2) or alpha(1)-adrenoreceptors and is manifested as an increase in the amplitude of XII nerve output due to an increase in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated motoneuronal drive currents. Blockade of Group 1 metabotropic glutamate receptors or protein kinase C (PKC) prevents the induction of ivLTF.