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Keywords:

  • brainstem;
  • DHPG;
  • hypoglossus nucleus;
  • respiration;
  • swallowing

Abstract

Group I metabotropic glutamate receptors (mGluRs) are the main class of metabotropic receptors expressed in the hypoglossus nucleus. Their role in glutamatergic transmission was investigated using patch-clamp recording from motoneurons in a neonatal rat brainstem slice preparation. After pharmacological block of γ-aminobutyric acid and glycine-mediated inhibition, under voltage-clamp, the selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induced a motoneuron inward current by depressing a leak conductance, and strongly facilitated spontaneous glutamatergic synaptic currents. This effect was blocked by 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) and unaffected by 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), indicating a role for subtype 1 mGluRs. The frequency but not the amplitude of miniature glutamatergic currents was also enhanced by DHPG. Currents elicited by puffer application of (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the presence of tetrodotoxin were also unchanged, suggesting that DHPG facilitated release of glutamate. Glutamatergic currents evoked by electrically stimulating the dorsomedullary reticular column premotoneurons were, however, depressed by DHPG in a CPCCOEt-sensitive fashion. Neither CPCCOEt nor MPEP per se changed glutamatergic transmission. Under current-clamp, even if DHPG depressed excitatory postsynaptic potentials, motoneuron spike threshold and time to peak were reduced so that facilitation of synaptic potential/spike coupling became apparent. We propose a wiring diagram to account for the differential action by DHPG on spontaneous and evoked transmission, based on the discrete distribution of subtype 1 mGluRs on glutamatergic afferents. Although under standard recording conditions there was insufficient ambient glutamate to activate mGluRs, such receptors were a powerful target to upregulate excitatory synaptic transmission and enhance signalling by hypoglossal motoneurons to tongue muscles.