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Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1763, USA

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.

(Received 5 September 2003; accepted after revision 2 December 2003; first published online 5 December 2003)
Corresponding author S. A. Saywell: Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1763, USA. Email: ssaywell{at}ucla.edu

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