Synaptically activated calcium responses in dendrites of hippocampal oriens-alveus interneurons

Activation of metabotropic glutamate receptors (mGluRs) by agonists increases intracellular calcium levels ([Ca²⁺]_i) in interneurons of stratum oriens/alveus (OA) of the hippocampus. We examined the mechanisms that contribute to dendritic Ca²⁺ increases in these interneurons during agonist activation of mGluRs and during synaptically evoked burst discharges, using simultaneous whole cell recordings and confocal Ca²⁺ imaging in rat hippocampal slices. First, we found that the group I/II mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 100 μM) increased dendritic [Ca²⁺]_i and depolarized OA interneurons. Dendritic Ca²⁺ responses were correlated with membrane depolarizations, but Ca²⁺ responses induced by ACPD were larger in amplitude than those elicited by equivalent somatic depolarization. Next, we used linescans to measure changes in dendritic [Ca²⁺ ]_i during synaptically evoked burst discharges and somatically elicited repetitive firing in disinhibited slices. Dendritic Ca²⁺ signals and electrophysiological responses were stable over repeated trials. Peak Ca²⁺ responses were linearly related to number and frequency of action potentials in burst discharges for both synaptic and somatic stimulation, but the slope of the relationship was steeper for responses evoked somatically. Synaptically evoked [Ca²⁺]_i rises and excitatory postsynaptic potentials were abolished by antagonists of ionotropic glutamate receptors. The group I/II mGluR antagonist S-α-methyl-4-carboxyphenylglycine (500 μM) produced a significant partial reduction of synaptically evoked dendritic Ca²⁺ responses. The mGluR antagonist did not affect synaptically evoked burst discharges and did not reduce either Ca²⁺ responses or burst discharges evoked somatically. Therefore ionotropic glutamate receptors appear necessary for synaptically evoked dendritic Ca²⁺ responses, and group I/II mGluRs may contribute partially to these responses. Dendritic [Ca²⁺]_i rises mediated by both ionotropic and metabotropic glutamate receptors may be important for synaptic plasticity and the selective vulnerability to excitotoxicity of OA interneurons.