Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

Abstract

SUMMARY1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CAI region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques.2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100 ,sM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential.3. Ibotenate (25 ,lM) or L-glutamate (250 /1M), in the presence of the N-methyl-Daspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75 JLM), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100 /tM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current.4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30 ,tM) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2 /,M).5. The response to ionophoretic application of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'.6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult ( > 80 days) slices.7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP).

Increasing age reduces expression of long-term depression and dynamic range of transmission plasticity in CA1 field of the rat hippocampus

“…The GABA B and adenosine A 1 receptor-induced presynaptic inhibition of EPSPs is of a rapid onset and fully reversible within 5-10 min after agonist application. 22,57 The depression of the fEPSPs produced by activation of the presynaptic metabotropic glutamate receptor, however, lasts more than 15 min after the termination of agonist application, 5,10,35 which is comparable to that elicited by LFS (see Fig. 2 for comparison).…”

“…15,23 The magnitude of LTP and LTD and/or depotentiation can be seen as reflecting the dynamic range of long-term modulation of transmission strength in glutamatergic synapses. 5 This dynamic range may be of significance for information processing by the hippocampus.…”

“…Although the stimulation protocol used, the receptors involved, and the magnitude and duration of expression are similar for depotentiation and LTD, 5 it is still uncertain whether LTD and depotentiation are indeed the same process, mediated by a same intracellular effector system. In addition, up to 24 months-of-age there is no significant decline in the magnitude of LTP expression in the CA1 field of the rat hippocampus, 12,13,27 although difficulties in induction of LTP in slices from rats older than 12 weeks have been reported.…”

Contribution of Cystine–Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

“…Studies utilizing microdialysis in the nucleus accumbens or electrophysiological recordings from acute prefrontal cortical or nucleus accumbens tissue slices indicate that nonvesicular glutamate release from cystineglutamate exchange stimulates extrasynaptic group II metabotropic glutamate receptors (mGluR) (Baker et al, 2002;Xi et al, 2002a;Moran et al, 2005). Because group II mGluRs function as autoreceptors (Baskys and Malenka, 1991;Cochilla and Alford, 1998;Hu et al, 1999b;Schoepp, 2001;Valenti et al, 2002;Xi et al, 2002b), extrasynaptic glutamate maintained by cystine-glutamate exchange negatively modulates synaptic release of glutamate (Moran et al, 2005). Since most studies focus on synaptic content, the failure to account for the presence of high, steady-state levels of glutamate in the extrasynaptic space represents a critical gap in attempts to model the contribution of excitatory neurotransmission to brain functioning in both the normal and diseased states.…”

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).…”