Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus

Abstract

1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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.…”

Trace Eyeblink Conditioning Increases CA1 Excitability in a Transient and Learning-Specific Manner

“…accommodation (Benardo and Prince, 1982;Haas and Konnerth, 1983;Haas and Greene, 1984;Madison and Nicoll, 1986;Colino and Halliwell, 1987;Hedlund and Andersen, 1989;Moyer et al, 1992;Liu et al, 1993). Decreased accommodation suggests that hippocampal neurons would be more likely to fire action potentials to excitatory afferent inputs and may reflect the demand for hippocampal processing required for acquisition or consolidation of the trace eyeblink conditioning task (Solomon et al, 1986;Moyer et al, 1990;Kim et al, 1995).…”

Activation of Group II Metabotropic Glutamate Receptors Inhibits the Discriminative Stimulus Effects of Alcohol via Selective Activity Within the Amygdala

“…mGlu2/3 receptors are members of the group II family of mGluRs. These G i -coupled receptors function as autoreceptors; regulating presynaptic neurotransmitter release (Baskys and Malenka, 1991;Liu et al, 1993;Macek et al, 1996;Marek et al, 2000;Molinaro et al, 2009;Farazifard and Wu, 2010). As such, activation of mGlu2/3 receptors decreases the synaptic availability of glutamate, allowing for 'refinement' of glutamatergic neurotransmission (Schoepp, 2001;Pinheiro and Mulle, 2008).…”