Activation of metabotropic glutamate receptors enhances synaptic transmission at the Drosophila neuromuscular junction

We examined the effects of activation of metabotropic glutamate receptors ( mGluRs) on glutamatergic synaptic transmission at the neuromuscular junctio n of newly hatched Drosophila larvae. In nominally Ca2+-free solutions puff -application of low concentrations of glutamate evoked a transient frequenc y increase of miniature synaptic currents (mSCs). The mean amplitude of mSC s was unaffected, suggesting that this effect was presynaptic. Similar alte rations of the mSC frequency were obtained using the mGluR agonists, (S)-4C 3HPG, DCG-IV, or (1S,3S)-ACPD, but not when using agonists for ionotropic g lutamate receptors) NMDA, AMPA or kainate. An mGluR antagonist, MCCG-I, blo cked the effect of agonists on the mSC frequency. An adenylate cyclase acti vator, forskolin, and a cAMP analog, CPT-cAMP, mimicked the effects of mGlu R activation. Meanwhile, an adenylate cyclase inhibitor, SQ22,536, blocked the mGluR agonist-induced effects, and in rutabaga, an adenylate-cyclase-de fective mutant, the effect of the agonist was greatly reduced. In the prese nce of external Ca2+, (S)-4C3HPG decreased the failure rate and increased t he mean amplitude of stimulus-evoked SCs, while MCCG-I decreased the amplit udes. We suggest that at the larval Drosophila neuromuscular junction endog enous glutamate released at the terminal potentiates synaptic transmission via a process involving cAMP. (C) 1999 Elsevier Science Ltd. All rights res erved.