INTERNEURON-SPECIFIC CA2+ RESPONSES LINKED TO METABOTROPIC AND IONOTROPIC GLUTAMATE RECEPTORS IN RAT HIPPOCAMPAL SLICES

Glutamate-mediated regulation of intracellular Ca2+ levels was examine d in different populations of CA1 interneurons, using confocal microsc opy and the Ca2+ indicator flue 3-AM in rat hippocampal slices. Intern eurons in basal [stratum oriens/alveus (OA)] and apical [strata radiat um and lacunosum-moleculare (R/LM)] dendritic layers responded heterog eneously to glutamate. In control medium, OA interneurons responded mo stly with oscillatory Ca2+ responses, which consisted of a large Ca2transient and successive smaller elevations. R/LM interneurons respond ed mostly with biphasic responses, characterized by an initial large t ransient and a secondary prolonged elevation. Other interneurons in bo th R/LM and OA responded with transient elevations in Ca2+ levels. Ion otropic glutamate receptor antagonists (+/-)2-amino-5-phosphonopentano ic acid and 6-cyano-7-nitro-quinoxaline-2,3-dione reduced peak Ca2+ re sponses in OA and R/LM cells, and blocked biphasic responses in R/LM i nterneurons, The metabotropic glutamate receptor antagonist (RS)-alpha -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 o scillatory responses were absent. Combination of ionotropic and metabo tropic receptor antagonists blocked all glutamate-evoked Ca2+ response s. Activation of different types of glutamate receptors may thus produ ce heterogeneous Ca2+ signals in subpopulations of CA1 interneurons. I onotropic receptors may generate biphasic responses in interneurons in apical dendritic layers, whereas combined activation of metabotropic and ionotropic receptors may trigger oscillatory responses in interneu rons of basal dendritic layers. These heterogeneous Ca2+ responses ind icate that glutamate-mediated Ca2+ processes and second messenger syst ems differ in subpopulations of hippocampal interneurons and suggest p ossible postsynaptic functional specialization of interneurons.