mGluR1/5 subtype-specific calcium signalling and induction of long-term potentiation in rat hippocampal oriens/alveus interneurones

摘要

Hippocampal inhibitory interneurones demonstrate pathway- and synapse-specific rules of transmission and plasticity, which are key determinants of their role in controlling pyramidal cell excitability. Mechanisms underlying long-term changes at interneurone excitatory synapses, despite their importance, remain largely unknown. We use two-photon calcium imaging and whole-cell recordings to determine the Ca~2+ signalling mechanisms linked specifically to group I metabotropic glutamate receptors (mGluRla and mGluR5) and their role in hebbian long-term potentiation (LTP) in oriens/alveus (O/A) interneurones. We demonstrate that mGluRla activation elicits dendritic Ca~2+ signals resulting from Ca~2+ influx via transient receptor potential (TRP) channels and Ca~2+ release from intracellular stores. By contrast, mGluR5 activation produces dendritic Ca~2+ transients mediated exclusively by intracellular Ca~2+ release. Using Western blot analysis and immunocytochemistry, we show mGluRla-specific extracellular signal-regulated kinase (ERK1/2) activation via Src in CA1 hippocampus and, in particular, in O/A interneurones. Moreover, we find that mGluRla/TRP Ca~2+ signals in interneurone dendrites are dependent on activation of the Src/ERK cascade. Finally, this mGluRla-specific Ca~2+ signalling controls LTP at interneurone synapses since blocking either TRP channels or Src/ERK and intracellular Ca~2+ release prevents LTP induction. Thus, our findings uncover a novel molecular mechanism of interneurone-specific Ca~2+ signalling, critical in regulating synaptic excitability in hippocampal networks.