Metabotropic glutamate receptors mediate a post‐tetanic excitation of guinea‐pig hippocampal inhibitory neurones.

Abstract

SUMMARY1. Inhibitory cell activity and inhibitory postsynaptic potentials impinging spontaneously on pyramidal cells were recorded in the CA3 region of hippocampal slices from guinea-pig. We compared the effects on synaptic inhibition, of tetanic stimuli in the presence of antagonists of ionotropic excitatory amino acid receptors, and of application of agonists of metabotropic glutamate receptors.2. Tetanic stimulation of afferent fibres caused an increase, of duration 0 52-5 min, in the frequency of spontaneous Cl--mediated IPSPs. Inhibitory cell firing increased due to a depolarization and a reduction of after-hyperpolarizing potentials.3. Tetanic stimulation induced, in some experiments, rhythmic bursts of IPSPs and transformed the firing pattern of some inhibitory cells from a discharge of single action potentials to rhythmic bursts of three to five action potentials.4. Application of the metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (tACPD), at concentrations from 3-10/,M increased the frequency of spontaneous IPSPs. In some slices tACPD caused IPSPs to occur rhythmically. IPSP

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

“…Thus, there is a clear-cut difference between interneuron subtypes that exhibit rhythmic firing (I and II) versus those that do not (III and IV), with frequent mGluR1 expression in the former and rare expression in the latter two classes. This observation is of particular interest in view of previous data indicating that the contribution of mGluRs to excitatory responses is significant only after activation by highfrequency stimuli (Bashir et al, 1993;Miles and Poncer, 1993). The evidence for the preferential extrasynaptic localization of mGluRs (Baude et al, 1993) is also indicative for a functional role of these glutamate receptors under conditions of highfrequency stimulation.…”

A Long-Lasting Calcium-Activated Nonselective Cationic Current Is Generated by Synaptic Stimulation or Exogenous Activation of Group I Metabotropic Glutamate Receptors in CA1 Pyramidal Neurons

“…In the hippocampus, activation of cationic currents through metabotropic receptors generates long-lasting plateau potentials (Fraser and MacVicar, 1996) and provides the basis for synchronized activities (Yaari and Jensen, 1989;Miles and Poncer, 1993;Bianchi and Wong, 1995). The synaptically activated I CAN described in the present report may play an important role in synaptic integration, notably as frequency sensors, in regard to its strong frequency dependence.…”

“…An accumulation of glutamate in the synaptic cleft and a "spillover" may be required to reach the perisynaptic receptors and trigger a mGluR-mediated response. Therefore, at least in CA1 pyramidal neurons I CAN probably does not participate in ongoing spontaneous activity; a different situation may prevail in interneurons (see Miles and Poncer, 1993).…”

Astrocyte Glutamate Transporters Regulate Metabotropic Glutamate Receptor-Mediated Excitation of Hippocampal Interneurons

“…In cultured hippocampal slices, stimulation of mGluR1 and mGluR5 also have been shown to potentiate inhibition of CA3 pyramidal neurons by increasing interneuron excitability (Maccaferri and Dingledine, 2002;Mori and Gerber, 2002), and, in acute slices from guinea pig, tetanic stimulation in the presence of AMPA and NMDA receptor antagonists induces a transient increase in IPSPs in CA3 pyramidal neurons (Miles and Poncer, 1993), indicating a prominent role for mGluRs in regulating interneuron activity. Under physiological conditions, even small shifts in the membrane potential of interneurons caused by moderate mGluR1 activity could serve as a mechanism for short-term regulation of local circuit inhibition, because the timing of action potential firing in these cells is highly sensitive to the resting potential (Freund and Buzsáki, 1996).…”