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

Abstract

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 mGluR1alpha isoform is characteristically expressed only by nonprincipal cells, and it is particularly enriched in somatostatin (SS)-containing interneurons in stratum oriensalveus. Anatomical and physiological data have indicated the presence of mGluR1alpha 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 mGluR1alpha by immunofluorescent labeling, combining antibodies to mGluR1alpha, calcium-binding proteins, and neuropeptides, and by intracellular labeling in vitro. Several types of interneuron that are immunopositive for mGluR1alpha each targeted different domains of pyramidal cells and included (1) O-LM inter-neurons, 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 oriens-bistratified cells. Estimation of the relative proportion of mGluR1alpha-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 mGluR1alpha provides the network basis for assessing the contribution of this receptor to the excitability of the hippocampus.

Target-Cell-Specific Left-Right Asymmetry of NMDA Receptor Content in Schaffer Collateral Synapses in ϵ1/NR2A Knock-Out Mice

“…4 B). However, these double-labeled interneurons had dendrites mostly localized to the alveus and adjoining stratum oriens but not to the stratum radiatum in CA1, resembling O-LM cells (Ferraguti et al, 2004).…”

“…However, these neurons contribute to only a minor subpopulation of the GluR4-immunopositive dendrites we examined because their dendrites are very sparse in stratum radiatum (Ferraguti et al, 2004). The GluR4-immunonegative interneuron dendrites may at least originate from calretinin-and calbindin-containing interneurons (Fig.…”

Metabotropic Glutamate Receptor 8-Expressing Nerve Terminals Target Subsets of GABAergic Neurons in the Hippocampus

“…Interneurons receiving mGluR8 innervation and positive for mGluR1a, SOM, and weakly for PV are probably O-LM cells Klausberger et al, 2003;Ferraguti et al, 2004). A few other mGluR8-decorated cells contained CR and may be IS (Freund and Buzsaki, 1996;Ferraguti et al, 2004).…”

“…Interneurons receiving mGluR8 innervation and positive for mGluR1a, SOM, and weakly for PV are probably O-LM cells Klausberger et al, 2003;Ferraguti et al, 2004). A few other mGluR8-decorated cells contained CR and may be IS (Freund and Buzsaki, 1996;Ferraguti et al, 2004). The rare calbindin-or CCK-positive neurons innervated by mGluR8 terminals may belong to the Schaffer collateral-associated interneurons expressing both CCK and calbindin (Cope et al, 2002).…”

“…Scale bars, 30 m. classes, which include O-LM cells, O-Bi cells, and interneurons selectively targeting other interneurons (IS) (Losonczy et al, 2002;Ferraguti et al, 2004). Because O-LM cells are known to express high levels of postsynaptic mGluR1a receptors (Baude et al, 1993), to contain both SOM and PV (Klausberger et al, 2003;Ferraguti et al, 2004) and also to be heavily decorated by mGluR7a-containing terminals (Shigemoto et al, , 1997, we performed a series of triple-immunolabeling experiments combining antisera for these markers (Table 1). Terminals containing mGluR8a immunoreactivity unevenly innervated mGluR1a-immunolabeled neurons expressing SOM as well as PV (Fig.…”