Differential regulation of metabotropic glutamate receptor- and AMPA receptor-mediated dendritic Ca2+ signals by presynaptic and postsynaptic activity in hippocampal Interneurons

Calcium plays a crucial role as a ubiquitous second messenger and has a key influence in many forms of synaptic plasticity in neurons. The spatiotemporal properties of dendritic Ca2+ signals in hippocampal interneurons are relatively unexplored. Here we use two- photon calcium imaging and whole- cell recordings to study properties of dendritic Ca2+ signals mediated by different glutamate receptors and their regulation by synaptic activity in oriens/ alveus ( O/ A) interneurons of rat hippocampus. We demonstrate that O/ A interneurons express Ca2+- permeable AMPA receptors ( CP- AMPARs) providing fast Ca2+ signals. O/ A cells can also coexpress CP- AMPARs, Ca2+ -impermeable AMPARs ( CI- AMPARs), and group I/ II metabotropic glutamate receptors ( mGluRs) ( including mGluR1a), in the same cell. CI- AMPARs are often associated with mGluRs, resulting in longer- lasting Ca2+ signals than CP- AMPAR- mediated responses. Finally, CP- AMPAR- and mGluR- mediated Ca2+ signals demonstrate distinct voltage dependence and are differentially regulated by presynaptic and postsynaptic activity: weak synaptic stimulation produces Ca2+ signals mediated by CP- AMPARs, whereas stronger stimulation, or weak stimulation coupled with postsynaptic depolarization, recruits Ca2+ signals mediated by mGluRs. Our results suggest that differential activation of specific glutamate receptor- mediated Ca2+ signals within spatially restricted dendritic microdomains may serve distinct signaling functions and endow oriens/ alveus interneurons with multiple forms of Ca2+- mediated synaptic plasticity. Specific activation of mGluR- mediated Ca2+ signals by coincident presynaptic and postsynaptic activity fulfills the conditions for Hebbian pairing and likely underlies their important role in long- term potentiation induction at O/ A interneuron synapses.