Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells

Gerber, Urs; Lüthi, Anita; Gähwiler, Beat H.

doi:10.1098/rspb.1993.0142

Cited by 22 publications

(3 citation statements)

References 19 publications

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“…As such, relatively long intracellular impalements were required to obtain meaningful data. This contrasts with metabotropic glutamate receptor-mediated EPSPs which can be evoked reproducibly every 30-60 s (Gerber, L uthi & G ahwiler, 1993). The reason(s) for the protracted fatigue of the EPSPm is unclear but by comparison with previous studies it appears to be independent of the stimulation protocol used to evoke it, i.e.…”

Section: Discussionmentioning

confidence: 43%

Regulation of muscarinic acetylcholine receptor‐mediated synaptic responses by adenosine receptors in the rat hippocampus

Morton¹,

Davies²

1997

The Journal of Physiology

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1. Intracellular current clamp recordings were made from CA1 pyramidal neurones in rat hippocampal slices. Experiments were performed in the presence of ionotropic glutamate receptor antagonists and ã-aminobutyric acid (GABA) receptor antagonists to block all fast excitatory and inhibitory synaptic transmission. A single stimulus, delivered extracellularly in the stratum oriens, caused a reduction in spike frequency adaptation in response to a depolarizing current step delivered 2 s after the stimulus. A 2-to 10-fold increase in stimulus intensity evoked a slow excitatory postsynaptic potential (EPSP) which was associated with a small increase in input resistance. The peak amplitude of the EPSP occurred approximately 2·5 s after the stimulus and its magnitude (up to 30 mV) and duration (10-50 s) increased with increasing stimulus intensity. 2. The slow EPSP was unaffected by the metabotropic glutamate receptor antagonist (+)-á-methyl-4-carboxyphenylglycine ((+)-MCPG; 1000 ìÒ) but was greatly enhanced by the acetylcholinesterase inhibitor physostigmine (1-5 ìÒ). Both the slow EPSP and the stimulus-evoked reduction in spike frequency adaptation were inhibited by the muscarinic acetylcholine receptor (mAChR) antagonist atropine (1-5 ìÒ). These results are consistent with these effects being mediated by mAChRs. 3. Both the mAChR-mediated EPSP (EPSPm) and the associated reduction in spike frequency adaptation were reversibly depressed (up to 97%) by either adenosine (100 ìÒ) or its nonhydrolysable analogue 2-chloroadenosine (CADO; 0·1-5·0 ìÒ). These effects were often accompanied by postsynaptic hyperpolarization (up to 8 mV) and a reduction in input resistance (up to 11%). The selective adenosine AÔ receptor agonists 2-chloro-NÉ-cyclopentyladenosine (CCPA; 0·1-0·4 ìÒ) and R(−)NÉ-(2-phenylisopropyl)-adenosine (R-PIA; 1 ìÒ) both depressed the EPSPm. In contrast, the adenosine A2A receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 0·5-1·0 ìÒ) did not significantly affect the EPSPm. 4. The selective adenosine AÔ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0·2 ìÒ) fully reversed the depressant effects of both adenosine (100 ìÒ) and CADO (1 ìÒ) on the EPSPm and the stimulus-evoked reductions in spike frequency adaptation. 5. DPCPX (0·2 ìÒ) alone caused a small but variable mean increase in the EPSPm of 22 ± 19% and enabled activation of an EPSPm by a previously subthreshold stimulus. In contrast, the selective adenosine kinase inhibitor 5-iodotubercidin (5-IT; 10 ìÒ) inhibited the EPSPm by 74 ± 10 %, an effect that was reversed by DPCPX. 6. The concentration-response relationship for the depressant action of CADO on the EPSPm more closely paralleled that for its presynaptic depressant action on glutamate-mediated EPSPs than that for postsynaptic hyperpolarization. The respective mean ICÛÑ and ECÛÑ concentrations for these effects were 0·3, 0·8 and 3·0 ìÒ. 7. CADO (1-5 ìÒ) did not have a significant effect on the postsynaptic depolarization, increase in input ...

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Section: Discussionmentioning

confidence: 43%

Regulation of muscarinic acetylcholine receptor‐mediated synaptic responses by adenosine receptors in the rat hippocampus

Morton¹,

Davies²

1997

The Journal of Physiology

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“…Like (+)-MCPG this compound is also a relatively weak antagonist of mGluRs (Watkins & Collingridge, 1994) and therefore was used at 1000 M4M. This profile of antagonism of mGluRs in CAl pyramidal neurones is similar to that of mGluRs which depolarize spinal cord motoneurones Eaton et al, 1993) and CA3 pyramidal neurones (Gerber et al, 1993;Guerineau et al, 1994). In the nucleus tractus solitarius (NTS), however, neither 250 gM (±)-MCPG nor 500 gM (SR)-4CPG reversed significantly an inward current induced by 25 gM (lS,3R)-ACPD (Glaum et al, 1993).…”

Section: Antagonist Pharmacologymentioning

confidence: 99%

Pharmacology of postsynaptic metabotropic glutamate receptors in rat hippocampal CA1 pyramidal neurones

Davies

Clarke

Jane

et al. 1995

British J Pharmacology

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Activation of metabotropic glutamate receptors (mGluRs) in hippocampal CA1 pyramidal neurones leads to a depolarization, an increase in input resistance and a reduction in spike frequency adaptation (or accommodation). At least eight subtypes of mGluR have been identified which have been divided into three groups based on their biochemical, structural and pharmacological properties. It is unclear to which group the mGluRs which mediate these excitatory effects in hippocampal CA1 pyramidal neurones belong. We have attempted to address this question by using intracellular recording to test the effects of a range of mGluR agonists and antagonists, that exhibit different profiles of subtype specificity, on the excitability of CA1 pyramidal neurones in rat hippocampal slices (2S,1′S,2′S)‐2‐(2′‐carboxycyclopropyl)glycine (L‐CCG1) caused a reduction in spike frequency adaptation and a depolarization (1–10 mV) associated with an increase in input resistance (10–30%) at concentrations (≥50 μm) that have been shown to activate mGluRs in groups I, II and III. Similar effects were observed with concentrations (50–100 μm) of (1 Inhibition of the release of endogenous neurotransmitters through activation of GABAB receptors, by use of 200 μm (±)‐baclofen, did not alter the effects of (1S,3R)‐ACPD (50‐100 μm) (1S,3S)‐ACPD (100 μm) or L‐CCG1 (100 μm). This suggests that mGluR agonists directly activate CA1 pyramidal neurones. Like these broad spectrum mGluR agonists, the racemic mixture ((SR)‐) or resolved (S)‐isomer of the selective group I mGluR agonist 3,5‐dihydroxyphenylglycine ((SR)‐DHPG (50‐100 μm) or (S)‐DHPG (20‐50μm)) caused a reduction in spike frequency adaptation concomitant with postsynaptic depolarization and an increase in input resistance. In contrast, 2S,1′R,2′R,3′R‐2‐(2′,3′‐dicarboxycyclo‐propyl)glycine (DCG‐IV; 100 μm) and (S)‐2‐amino‐4‐phosphonobutanoic acid (L‐AP4; 100‐500 μm), which selectively activate group II mGluRs and group III mGluRs, respectively, had no effect on the passive membrane properties or spike frequency adaptation of CA1 pyramidal neurones. The mGluR antagonists (+)‐α‐methyl‐4‐carboxyphenylglycine ((+)‐MCPG; 1000 μm) and (S)‐4‐carboxyphenylglycine ((S)‐4CPG; 1000 μm), which block groups I and II mGluRs and group I mGluRs, respectively, had no effect on membrane potential, input resistance or spike frequency adaptation per se. Both of these antagonists inhibited the postsynaptic effects of (1S,3R)‐ACPD (50‐100 μm), (1S,3S)‐ACPD (30‐100 μm) and L‐CCG1 (50‐100 μm). (+)‐MCPG also reversed the effects of (SR)‐DHPG (75 μm). (The effect of (S)‐4CPG was not tested.) Their action was selective in that both antagonists did not reverse the reduction in spike frequency adaptation induced by carbachol (1 μm) or noradrenaline (10 μm) whereas atropine (10 μm) and propranolol (100 μm) did. From these data it is concluded that the mGluRs in CA1 pyramidal neurones responsible for these excitatory effects are similar to the mGluRs expressed by non‐neuronal cells transfected with cDNA encoding group I mGluRs.

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“…2), suggests that the observed effects of Gly and Ser are due either to Gly-and Ser-induced sensibilization of mGR to glutamate released from presynaptic terminals following SchC activation by single stimulus, or to mGR activation, which modulates synaptic transmission. However, a single stimulus applied to presynaptic inputs does not result in synaptic activation of mGR, which is observed only when rhythmic stimulation is applied [13]. Therefore, it seems more likely that Gly and Ser, similarly to glutamate, activate mGR.…”

Section: Discussionmentioning

confidence: 97%

Glycine and serine as tentative agonists for metabotropic glutamate receptors

et al. 1997

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In experiments on slices of the rat hippocampus, glycine (Gly) and serine (Ser) in concentrations of 100/~M to 1 mM were found to reversibly increase the amplitudes of population EPSP (pEPSP) in pyramidal neurons of the CA1 hippocampal area, evoked by single electrical stimuli applied to Schaffer collaterals (SchC). This potentiation was not affected by 100/zM of a non-competetive antagonist of NMDA glutamate receptors (GR), ketamine, but was considerably weakened by 500 /~M of a competitive antagonist of metabotropic GR (mGR), (• boxyphenylglycine (CFG). The effects of Gly and Ser were not observed in the presence of 50/~M of a blocker of protein kinase C (PKC) catalytic subunit, polymixin B, hut were not modified by preliminary action on the slices of 10 /~M of a calmodulin inhibitor, substance W-7. Gly and Ser also enhanced long-term post-tetanic potentiation (LTPP) of synaptic transmission caused by high-frequency rhythmic stimulation of SchC. Low-frequency (1/sec, 15 rain) SchC stimulation abolished the potentiation of synaptic transmission evoked either by high-frequency SchC stimulation or by the actions of Gly and Set. The data allow us to suggest that Gly and Ser in millimolar concentrations activate mGR, enhance relay functions of the synapses of pyramidal neurons in the CAI hippocampal region, and facilitate plastic modifications in these synapses.

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Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells

Cited by 22 publications

References 19 publications

Regulation of muscarinic acetylcholine receptor‐mediated synaptic responses by adenosine receptors in the rat hippocampus

Regulation of muscarinic acetylcholine receptor‐mediated synaptic responses by adenosine receptors in the rat hippocampus

Pharmacology of postsynaptic metabotropic glutamate receptors in rat hippocampal CA1 pyramidal neurones

Glycine and serine as tentative agonists for metabotropic glutamate receptors

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