Interneuron-specific Ca²⁺ responses linked to metabotropic and ionotropic glutamate receptors in rat hippocampal slices

Glutamate-mediated regulation of intracellular Ca²⁺ levels was examined in different populations of CA1 interneurons, using confocal microscopy and the Ca²⁺ indicator fluo 3-AM in rat hippocampal slices. Interneurons in basal [stratum oriens/alveus (OA)] and apical [strata radiatum and lacunosum-moleculare (R/LM)] dendritic layers responded heterogeneously to glutamate. In control medium, OA interneurons responded mostly with oscillatory Ca²⁺ responses, which consisted of a large Ca²⁺ transient and successive smaller elevations. R/LM interneurons responded mostly with biphasic responses, characterized by an initial large transient and a secondary prolonged elevation. Other interneurons in both R/LM and OA responded with transient elevations in Ca²⁺ levels. Ionotropic glutamate receptor antagonists (±)2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitro-quinoxaline-2,3-dione reduced peak Ca²⁺ responses in OA and R/LM cells, and blocked biphasic responses in R/LM interneurons. The metabotropic glutamate receptor antagonist (RS)-α-methyl-4-carboxyphenylglycine reduced peak Ca²⁺ responses only in OA interneurons, and prevented oscillatory responses. In low Ca²⁺ medium, peak responses were reduced in R/LM but not in OA interneurons, and oscillatory responses were absent. Combination of ionotropic and metabotropic receptor antagonists blocked all glutamate-evoked Ca²⁺ responses. Activation of different types of glutamate receptors may thus produce heterogeneous Ca²⁺ signals in subpopulations of CA1 interneurons. Ionotropic receptors may generate biphasic responses in interneurons in apical dendritic layers, whereas combined activation of metabotropic and ionotropic receptors may trigger oscillatory responses in interneurons of basal dendritic layers. These heterogeneous Ca²⁺ responses indicate that glutamate-mediated Ca²⁺ processes and second messenger systems differ in subpopulations of hippocampal interneurons and suggest possible postsynaptic functional specialization of interneurons.