Metabotropic glutamate receptors and blockade of glial Krebs cycle depressglycinergic synaptic currents of mouse hypoglossal motoneurons

Metabotropic glutamate receptors are known to depress synaptic transmission by inhibiting transmitter release from presynaptic nerve terminals. This s tudy reports the effects of presynaptic metabotropic glutamate receptor act ivation on inhibitory synaptic transmission in hypoglossal motoneurons in b rainstem slice preparations of neonatal mice. Whole-cell patch-clamp record ings were performed on hypoglossal motoneurons of 2-6-day-old mice. Monosyn aptic glycinergic currents were elicited by electrical stimulation of the n ucleus of Roller. Application of the specific metabotropic glutamate recept or agonists (+/-)-1-aminocyclopentane-trans-1,3,dicarboxylic acid (t-ACPD), (2s,2'R,3'R)-2-(2',3'-dicarboxylcyclopropyl)-glycine (DCG-IV) or L-2-amino -4-phosphonobutyric acid (L-AP4) depressed stimulus-evoked glycinergic inhi bitory postsynaptic currents (IPSCs) by an average of 39.5, 59.4 and 39.2%, respectively. In the presence of t-ACPD, glycinergic miniature IPSCs were reduced in frequency but not in amplitude, which is indicative of a presyna ptic mechanism. A similar reduction of IPSC amplitude was observed in the p resence of elevated extracellular glutamate or during application of D,L-th reo-hydroxyaspartate (THA), a blocker of glutamate transport, respectively. The data suggest that uptake of glutamate, which is predominately carried out by glial cells, can prevent spill-over of glutamate and activation of m etabotropic glutamate receptors. A reduction of IPSCs was also observed fol lowing application of monofluoroacetic acid, a substance acting specificall y on glial cells. Our results suggest that glial regulation of extracellula r glutamate uptake can prevent spillover of glutamate, and glutamatergic de pression of glycinergic inhibition in hypoglossal motoneurons.