Dynamic interactions of excitatory and inhibitory inputs in hypoglossal motoneurones: respiratory phasing and modulation by PKA.
The balance of excitation and inhibition converging upon a neurone is a principal determinant of neuronal output. We investigated the role of inhibition in shaping and gating inspiratory drive to hypoglossal (XII) motoneuronal activity. In neonatal rat medullary slices that generate a spontaneous respiratory rhythm, patch-clamp recordings were made from XII motoneurones, which were divided into three populations according to their inhibitory inputs: non-inhibited, inspiratory-inhibited and late-inspiratory-inhibited. In late-inspiratory-inhibited motoneurones, blockade of GABA(A) receptors with bicuculline abolished inspiratory-phased inhibition and increased the duration of inspiratory drive currents. In inspiratory-inhibited motoneurones, bicuculline abolished phasic inhibition, which frequently revealed excitatory inspiratory drive currents. In non-inhibited motoneurones, neither bicuculline nor strychnine markedly changed inspiratory drive currents. Inhibitory currents in XII motoneurones were potentiated by protein kinase A (PKA) activity. Intracellular dialysis of the catalytic subunit of PKA or bath application of the PKA activator Sp-cAMP significantly increased the amplitude of expiratory-phased IPSCs without any change in IPSP frequency. Inspiratory-phased inhibition in inspiratory-inhibited motoneurones was potentiated by Sp-cAMP. We conclude that inspiratory-phased inhibition is prevalent in neonatal XII motoneurones and plays an important role in shaping motoneuronal output. These inhibitory inputs are modulated by PKA, which also modulates excitatory inputs.
Saywell
Shane A
SA
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1763, USA. ssaywell@ucla.edu
Feldman
Jack L
JL
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D045853:Exhalation / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D001239:Inhalation / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology*; D013569:Synapses / Q000502:physiology
D018756:GABA Antagonists; D017868:Cyclic AMP-Dependent Protein Kinases