Enhanced Sensitivity of "Metabotropic" Glutamate Receptors After Induction of Long-Term Potentiation in Rat Hippocampus (original) (raw)
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Pharmacological Research, 1990
InsP) formation by ibotenate or trans-1 -aminocyclopentyl-1,3-dicarboxylic acid (t-ACPD) in rat hippocampal slices was enhanced after tetanic stimulation of the SchaRer collaterals projecting to the CA 1 region (in vitro) or the perforant pathway projecting to the dentate gyrus (in freely moving animals). This effect was observed 5 h (but not 2 h) after long-term potentiation (LTP) induction and was abolished if tetanic stimulation was performed in the presence of specific antagonists of N-methyl-D-aspartate receptors. The delayed increase in excitatory amino acid-induced polyphosphoinositide (PPI) hydrolysis was accompanied by an enhanced responsiveness to norepinephrine, whereas the basal and carbamylcholine-stimulated [3H]InsP formation were unchanged. These results suggest that an increased activity of "metabotropic" glutamate receptors may contribute to the synaptic mechanisms enabling the late expression and or maintenance of LTP. Accordingly, LTP decayed more rapidly (within 5 h) in rats repeatedly injected with LiCl (60-120 mg/kg, i.p., for 10 days), a treatment that led to a reduced efficacy of ibotenate and norepinephrine in stimulating PPI hydrolysis in hippocampal slices. Key Words: Glutamate-Phosphoinositides-Long-term potentiation-Hippocampus. Aronica E. et al. Enhanced sensitivity of "metabotropic" glutamate receptors after induction of long-term potentiation in rat hippocampus. Abbreviations used: t-ACPD, trans-aminocyclopentyl-1,3-dicarboxylic acid; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazolpro-
Neuroscience, 1993
Slices of hippocampal area CA1 in the rat were employed to test the hypothesis that the activation of metabotropic glutamate receptors during tetanization is necessary for the late maintenance of long-term potentiation. If the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate was present during tetanization, post-tetanic and early long-term potentiation of the population spike as well as field excitatory postsynaptic potential developed almost normally. However, 100 min after tetanization, long-term potentiation of the field excitatory postsynaptic potential decreased in an irreversible manner. The same concentration of D-2-amino-3-phosphonopropionate was ineffective. If L-2-amino-3phosphonopropionate was applied 120 min after tetanization, it did not influence long-term potentiation. The presence of the metabotropic glutamate receptor agonist rrans-D,L-1-aminocyclopentane-1,3-dicarboxylic acid during tetanization weakly enhanced the slope of field excitatory postsynaptic potential long-term potentiation. The influence of L-2-amino-3-phosphonopropionate and D,L-1-amhiocyclopentane-1,3-dicarboxylic acid on ionotropic glutamate receptors was studied using whole-cell voltage-clamp and pressure application techniques. No effect of L-2-amino-3-phosphonopropionate on either early or late components of excitatory postsynaptic currents could be detected at the concentration used to block long-term potentiation. It is therefore unlikely that the effect of L-2-amino-3-phosphonopropionate on long-term potentiation is due to an interaction with N-methyl-D-aspartate receptors or a-amino-3hydroxy-S-methyl-4-isoxazole propionic acid receptors. However, bath-applied lS,3R-D,L-l-aminocyclopentane-l,3-dicarboxylic acid facilitated the N-methyl-D-aspartate-induced depolarization in response to N-methyl-o-aspartate pressure application in a reversible manner.
Neuroscience, 1998
In this study, the role of metabotropic glutamate receptors in N-methyl--aspartate receptordependent and voltage-gated calcium channel-dependent long-term potentiation in the dentate gyrus of freely moving rats was investigated. Antagonists for group 1 metabotropic glutamate receptors ((S)-4-carboxyphenylglycine), group 1/2 metabotropic glutamate receptors ((RS)-methyl-4-carboxyphenylglycine) and group 2 metabotropic glutamate receptors ((RS)-methylserine O-phosphate monophenylester) were used. The N-methyl--aspartate receptor antagonist, ()-2-amino-5-phosphonopentanoic acid, and the L-type voltage-gated calcium channel antagonist, methoxyverapamil were used to investigate the N-methyl--aspartate receptor and voltage-gated calcium channel contribution to the long-term potentiation recorded. Field excitatory postsynaptic potential slope and population spike amplitude were measured. Drugs were applied, prior to tetanus, via a cannula implanted into the lateral cerebral ventricle. 200 Hz tetanization produces a long-term potentiation which is inhibited by application of ()-2-amino-5-phosphonopentanoic acid and (RS)-methyl-4-carboxyphenylglycine. In this study, a dose-dependent inhibition of 200 Hz long-term potentiation expression was obtained with (S)-4carboxyphenylglycine. Long-term potentiation induced by 400 Hz tetanization was not inhibited by ()-2-amino-5-phosphonopentanoic acid, although the amplitude of short-term potentiation was reduced. (RS)-methyl-4-carboxyphenylglycine and (S)-4-carboxyphenylglycine, both in the presence and absence of ()-2-amino-5-phosphonopentanoic acid, inhibited the development of 400 Hz long-term potentiation. (RS)-methylserine O-phosphate monophenylester had no significant effect on long-term potentiation induced by either 200 or 400 Hz tetanization. Application of methoxyverapamil significantly inhibited 400 Hz long-term potentiation, but had no effect on 200 Hz long-term potentiation. These data suggest that 400 Hz long-term potentiation, induced in the presence of ()-2-amino-5phosphonopentanoic acid, requires activation of L-type calcium channels. Furthermore, these results strongly support a critical role for group 1 metabotropic glutamate receptors in both N-methyl-aspartate receptor-and voltage-gated calcium channel-dependent long-term potentiation. 1998 IBRO.
Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats
Brain Research Bulletin, 2002
Rats subjected to monosodium glutamate (MSG) administration during the neonatal period present chronic neuroendocrine dysfunction associated with marked cognitive deficits. Long-term potentiation (LTP) in the hippocampus provides a model suited for the study of mammalian brain plasticity and memory formation. In the present work, we used the LTP protocol to investigate the synaptic plasticity in the hippocampal CA1 area of adult rats subjected to MSG treatment during the first 10 days of life. Synaptic transmission in CA1 area was analyzed using extracellular field recordings in response to Schaffer's collateral fiber stimulation in hippocampal slices. Animals injected with MSG exhibited a dramatic decrement of LTP field excitatory postsynaptic potentials (fEPSPs) compared to control group. Analysis of percent enhancement of fEPSP slope at 2 min after high frequency stimulation (HFS) increased by 189.3 ± 33.2% in slices from control rats and 129.45±18.5% (p < 0.01) in slices from MSG-treated rats. Additionally, MSG-treated animals failed to maintain or consolidate LTP as revealed by a significant reduction in fEPSP slope enhancement over time after HFS. The mean fEPSP slope, 60 min after HFS, was 154.28 ± 21% of the average baseline slope in control slices versus only 124.4 ± 15% in MSG-treated rats (p < 0.01). At 90 min after HFS, slices from controls reached a potentiation of 44.5 ± 2.9%, whereas the MSG group displayed an overall response enhancement of 17.65 ± 2.7% of basal levels (p < 0.01). These findings indicate that MSG-treated rats display a chronic impairment of CA1 synaptic plasticity.
Neuroscience, 1999
We investigated mechanisms involved in the modulation of long-term potentiation by low concentrations of N-methyl-d-aspartate in the CA1 region of rat hippocampal slices. When applied for 5 min prior to and during tetanic stimulation, 1 mM N-methyl-d-aspartate inhibited long-term potentiation induction. Studies examining paired-pulse facilitation of non-N-methyl-d-aspartate receptor-mediated synaptic responses suggest that the effects of N-methyl-d-aspartate result in part from a presynaptic mechanism. This conclusion is supported by the observation that 1 mM N-methyl-d-aspartate failed to diminish N-methyl-d-aspartate receptor-mediated synaptic currents and that agents that enhance glutamate release, including high extracellular concentrations of calcium and an adenosine A1 receptor antagonist, overcome the long-term potentiation inhibition. Furthermore, the calcineurin inhibitors, FK-506 and cyclosporin A, as well as the phosphatase 1 and 2A inhibitor, okadaic acid, blocked the effects of Nmethyl-d-aspartate on long-term potentiation suggesting a role for phosphatase activation in modulating the induction of long-term potentiation. These results show that the inhibition of long-term potentiation by untimely N-methyl-d-aspartate receptor activation is reversed by treatments that enhance glutamate release and suggest that adenosine release and diminished calcium influx during tetanic stimulation coupled with phosphatase activation contribute to the modulation of synaptic plasticity.
Proceedings of the National Academy of Sciences, 1993
Several lines of evidence indicate that LTP in the hippocampus is associated with a change in the properties of postsynaptic glutamate receptors. In the present study, we used quantitative autoradiography to examine the binding properties of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate subclasses of glutamate receptors in frozen brain sections obtained from rats in which perforant-path LTP was induced in vivo. Induction of LTP resulted in a selective increase in [3H]AMPA binding in those hippocampal subfields receiving perforant-path axons.
European Journal of Pharmacology, 1995
The effects of two competitive metabotropic glutamate (mGlu) receptor antagonists, (RS)-a-methyl-4-carboxyphenylglycine (MCPG) and (S)-4-carboxylphenylglycine (4CPG), were studied on long-term potentiation in the dentate gyrus of rats under urethane anaesthesia, lntracerebroventricular (i.c.v.) injection of MCPG or 4CPG 30 min prior to tetanic stimulation of the perforant path in rats did not affect the induction of long-term potentiation measured by extracellular recording. As a control, i.c.v, injections of the NMDA receptor antagonist, dl(-)-2-amino-5-phosphonopentanoic (dl-AP5), effectively blocked long-term potentiation. These results suggest that the mGlu receptor subtype blocked by MCPG and 4CPG is not involved in long-term potentiation in the dentate gyrus.