Differential Expression of Group I Metabotropic Glutamate Receptors in Functionally Distinct Hippocampal Interneurons

Abstract

Metabotropic glutamate receptors (mGluRs) have been proposed to be involved in oscillatory rhythmic activity in the hippocampus. However, the subtypes of mGluRs involved and their precise distribution in different populations of interneurons is unclear. In this study, we combined functional analysis of mGluR-mediated inward currents in CA1 oriens-alveus interneurons with anatomical and immunocytochemical identification of these interneurons and expression analysis of group I mGluR using single-cell reverse transcription-PCR (RT-PCR). Four major interneuron subtypes could be distinguished based on the mGluR-mediated inward current induced by the application of 100 M trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) under voltage-clamp conditions and the action potential firing pattern under current-clamp conditions. Type I interneurons responded with a large inward current of ϳ224 pA, were positive for somatostatin, and the majority expressed both mGluR1 and mGluR5. Type II interneurons responded with an inward current of ϳ80 pA, contained calbindin, and expressed mainly mGluR1. Type III interneurons responded with an inward current of ϳ60 pA. These interneurons were fast-spiking, contained parvalbumin, and expressed mainly mGluR5. Type IV interneurons did not respond with an inward current upon application of ACPD, yet they expressed group I mGluRs. Activation of group I mGluRs under currentclamp conditions increased spike frequency and resulted in rhythmic firing activity in type I and II, but not in type III and IV, interneurons. RT-PCR results suggest that activation of mGluR1 in the subsets of GABAergic interneurons, classified here as type I and II, may play an important role in mediating synchronous activity.

A hebbian form of long-term potentiation dependent on mGluR1a in hippocampal inhibitory interneurons

“…Second, LTP in interneurons involves the mGluR1a subtype of receptors. Finally, our preliminary data † and recent work of others (36) suggest that group I mGluR activity is associated with Ca 2ϩ responses and inward currents in oriens interneurons. Thus, mGluR1a, and not group II͞III mGluRs, may be critical for NMDAR-independent LTP in interneurons.…”

Endogenous Activation of Metabotropic Glutamate Receptors Modulates GABAergic Transmission to Gonadotropin-Releasing Hormone Neurons and Alters Their Firing Rate: A Possible Local Feedback Circuit

“…mGluRs modulate neurotransmission, acting presynaptically to reduce transmission at glutamatergic and GABAergic synapses (Glaum and Miller, 1993;Liu et al, 1993;Schoepp and Conn, 1993;Desai et al, 1994;McBain et al, 1994;Chu and Hablitz, 1998;van Hooft et al, 2000). In other brain regions, excitatory glutamate effects may be in part attributable to a concomitant reduction in inhibitory GABAergic drive through this mechanism.…”

Effects of subtype-selective group I mGluR antagonists on synchronous activity induced by 4-aminopyridine/CGP 55845 in adult guinea pig hippocampal slices

“…There are several mechanisms by which activation of mGlu5 receptors could decrease GPSP rate. It is known that mGlu5 receptors exist on some hippocampal interneurons (Romano et al, 1995;Luján et al, 1996;van Hooft et al, 2000) and on CA3 pyramidal cells (Romano et al, 1995;Luján et al, 1996). Even though the generation of GPSPs is primarily an interneuron network phenomenon (Michelson and Wong, 1991), and iGluR activation was not required for the generation of spontaneous GPSPs, iGluR antagonists did decrease GPSP rate, indicating that some portion of the GPSPs are probably triggered by a synchronous iGluR-mediated input, as suggested by the electrophysiological recordings.…”

“…One possible reason for differential effects would be if mGlu5 but not mGlu1 receptors were present at the locus of action. Both mGlu1 and mGlu5 receptors are present on CA3 pyramidal cells (Luján et al, 1996); however, some hippocampal interneurons express mGlu5 receptors and not mGlu1 receptors (van Hooft et al, 2000). A locus of action at CA3 interneurons expressing exclusively the mGlu5 subtype of group I mGluR would thus be one explanation.…”