Immunolocalization of metabotropic glutamate receptor 1α (mGluR1α) in distinct classes of interneuron in the CA1 region of the rat hippocampus

In the hippocampal CA1 region, metabotropic glutamate subtype 1 (mGluR1) receptors have been implicated in a variety of physiological responses to glutamate, which include modulation of synaptic transmission and plasticity, as well as neuronal excitability and synchronization. The mGluR1α isoform is characteristically expressed only by nonprincipal cells, and it is particularly enriched in somatostatin (SS -containing interneurons in stratum oriens-alveus. Anatomical and physiological data have indicated the presence of mGluR1α in several distinct classes of interneurons with their somata located also in strata pyramidale, radiatum, and lacunosum moleculare. Each different interneuron subtype, as defined by functionally relevant criteria, including input/output characteristics and expression of selective molecular markers, subserves distinct functions in local hippocampal circuits. We have investigated which of the different CA1 interneuron classes express mGluR1α by immunofluorescent labeling, combining antibodies to mGluR1α, calcium-binding proteins, and neuropeptides, and by intracellular labeling in vitro. Several types of interneuron that are immunopositive for mGluR1α each targeted different domains of pyramidal cells and included (1) O-LM interneurons, found to coexpress both SS and parvalbumin (PV); (2) interneurons with target selectivity for other interneurons, expressing vasoactive intestinal polypeptide (VIP) and/or the calcium-binding protein calretinin; (3) procholecystokinin-immunopositive interneurons probably non-basket and dendrite-targeting; and (4) an as-yet unidentified SS-immunoreactive but PV-immunonegative interneuron class, possibly corresponding to oriensbistratified cells. Estimation of the relative proportion of mGluR1α-positive interneurons showed 43%, 46%, and 30% co-labeling with SS, VIP, or PV, respectively. The identification of the specific subclasses of CA1 interneurons expressing mGluR1α provides the network basis for assessing the contribution of this receptor to the excitability of the hippocampus.