NOVEL GLIAL-NEURONAL SIGNALING BY COACTIVATION OF METABOTROPIC GLUTAMATE AND BETA-ADRENERGIC RECEPTORS IN RAT HIPPOCAMPUS

1. We have previously reported that activation of group II-like metabo tropic glutamate receptors (mGluRs) in rat hippocampus results in a po tentiation of the accumulation of cAMP elicited by activation of G-pro tein G(s)-coupled receptors. This large increase in cAMP levels result s in release of cAMP or a cAMP metabolite and depression of synaptic t ransmission at the Schaffer collateral-CA1 pyramidal cell synapse thro ugh activation of A(1) adenosine receptors. 2. Consistent with these s tudies, we report that antagonists of group II mGluRs block both the p otentiation of cAMP accumulation elicited by activation of mGluRs and the depression of synaptic transmission induced by coactivation of mGl uRs and beta-adrenergic receptors. 3. In situ hybridization studies su ggest that of the cloned group II mGluRs only mGluR-3 mRNA is present in area CA1. Interestingly, mGluR-3 appears to be present predominantl y in glia in this region. Thus, we tested the hypothesis that mGluRs c oupled to potentiation of cAMP accumulation were present on glia rathe r than neurons in area CA1. 4. The selective group II mGluR agonist S, 1'R,2'R,3'R-2-(2,3-dicarboxycyclo-propyl)glycine (DCG-IV) failed to en hance cAMP-mediated electrophysiological responses to the beta-adrener gic receptor agonist isoprenaline (Iso) in CA1 pyramidal cells, sugges ting that mGluRs coupled to potentiation of cAMP accumulation may not be present in these cells. 5. Pre-incubation of hippocampal slices wit h either of the selective glial toxins L-alpha-amino-adipic acid (L-AA ) or fluorocitrate (PC) blocked mGluR-mediated potentiation of cAMP ac cumulation. However, L-AA and FC had no discernible effects on viabili ty of CA1 pyramidal cells, or cAMP-mediated electrophysiological effec ts in these neurons. 6. Pre-incubation of hippocampal slices with the neurotoxin kainate resulted in disruption of neuronal transmission and degeneration of neurons in area CA1, but had no effect on mGluR-media ted potentiation of cAMP accumulation. 7. Pre-incubation of hippocampa l slices with the cAMP/cAMP metabolite transport blocker probenicid bl ocked the depression of synaptic transmission elicited by coapplicatio n of Iso and DCG-IV, while having no significant effect on cAMP accumu lation elicited by these agonists. 8. Taken together, these data sugge st that mGluRs coupled to potentiation of cAMP accumulation are presen t on glia rather than neurons in area CA1 of hippocampus. This suggest s that a novel form of glial-neuronal communication may exist, since a ctivation of these mGluRs in concert with beta-adrenergic receptors re sults in depression of synaptic transmission.