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. 1996 Aug 1;494(Pt 3):743–755. doi: 10.1113/jphysiol.1996.sp021529

Novel glial-neuronal signalling by coactivation of metabotropic glutamate and beta-adrenergic receptors in rat hippocampus.

D G Winder 1, P S Ritch 1, R W Gereau 4th 1, P J Conn 1
PMCID: PMC1160674  PMID: 8865071

Abstract

1. We have previously reported that activation of group II-like metabotropic glutamate receptors (mGluRs) in rat hippocampus results in a potentiation of the accumulation of cAMP elicited by activation of G-protein Gs-coupled receptors. This large increase in cAMP levels results in release of cAMP or a cAMP metabolite and depression of synaptic transmission at the Schaffer collateral-CA1 pyramidal cell synapse through activation of A1 adenosine receptors. 2. Consistent with these studies, we report that antagonists of group II mGluRs block both the potentiation of cAMP accumulation elicited by activation of mGluRs and the depression of synaptic transmission induced by coactivation of mGluRs and beta-adrenergic receptors. 3. In situ hybridization studies suggest that of the cloned group II mGluRs only mGluR-3 mRNA is present in area CA1. Interestingly, mGluR-3 appears to be present predominantly in glia in this region. Thus, we tested the hypothesis that mGluRs coupled to potentiation of cAMP accumulation were present on glia rather than neurons in area CA1. 4. The selective group II mGluR agonist 2S,1'R,2'R,3'R-2(2,3-dicarboxycyclo-propyl)glycine (DCG-IV) failed to enhance cAMP-mediated electrophysiological responses to the beta-adrenergic receptor agonist isoprenaline (Iso) in CA1 pyramidal cells, suggesting that mGluRs coupled to potentiation of cAMP accumulation may not be present in these cells. 5. Pre-incubation of hippocampal slices with either of the selective glial toxins L-alpha-aminoadipic acid (L-AA) or fluorocitrate (FC) blocked mGluR-mediated potentiation of cAMP accumulation. However, L-AA and FC had no discernible effects on viability of CA1 pyramidal cells, or cAMP-mediated electrophysiological effects 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-mediated potentiation of cAMP accumulation. 7. Pre-incubation of hippocampal slices with the cAMP/cAMP metabolite transport blocker probenicid blocked the depression of synaptic transmission elicited by coapplication of Iso and DCG-IV, while having no significant effect on cAMP accumulation elicited by these agonists. 8. Taken together, these data suggest that mGluRs coupled to potentiation of cAMP accumulation are present on glia rather than neurons in area CA1 of hippocampus. This suggests that a novel form of glial-neuronal communication may exist, since activation of these mGluRs in concert with beta-adrenergic receptors results in depression of synaptic transmission.

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Selected References

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