Group I metabotropic glutamate receptor activation reduces mEPSC frequency, but not amplitude, in cultured rat hippocampal neurones

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  • Group I metabotropic glutamate receptor activation reduces mEPSC frequency, but not amplitude, in cultured rat hippocampal neurones

University of Bristol (2001) J Physiol 536P, S180

Communications: Group I metabotropic glutamate receptor activation reduces mEPSC frequency, but not amplitude, in cultured rat hippocampal neurones

S.M. Fitzjohn†‡, J.E.R. May†, A. Neeson† and G.L. Collingridge†

†MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD and ‡ School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK

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Activation of group I metabotropic glutamate (mGlu) receptors by the agonist (RS)-3,5-dihydroxy-phenyl-glycine (DHPG) elicits a long-term depression (LTD) of synaptic transmission in the CA1 region of juvenile rat hippocampal brain slices (Fitzjohn et al. 1999). The mechanism underlying this form of synaptic plasticity, however, remains unclear. Here we have used cultures of dissociated rat hippocampal neurones to investigate the effect of DHPG on tetrodotoxin-resistant miniature excitatory postsynaptic currents (mEPSCs).

Cultures were prepared using the CA1-CA3 regions from 3- to 5-day-old Wistar rats. Rats were killed in accordance with Home Office regulations by decapitation and cultures were used 6-14 days after plating. Whole-cell recordings were made from the soma of pyramidal neurones voltage-clamped at -70 mV. After obtaining a stable baseline period, cells were perfused with DHPG-containing HBS (100 µM for 5 min).

Application of DHPG resulted in a sustained decrease in the frequency but not the amplitude of mEPSCs (n = 5). Thus 30 min after commencing washout of DHPG, mEPSC frequency was reduced to 61 ± 8 % of that recorded prior to application of DHPG (mean ± S.E.M.). Amplitude immediately prior to, and 30 min after commencing washout of, DHPG was 45 ± 8 and 49 ± 10 pA, respectively. Cumulative probability plots reveal a significant increase in inter-event interval after DHPG application (P < 0.05) but no change in mEPSC amplitude (P > 0.5; Kolmorogov-Smirnov test).

These data are consistent with a decrease in the probability of glutamate release underlying DHPG-induced LTD. Given the predominantly postsynaptic localisation of these receptors it is possible that a retrograde messenger is involved in this form of LTD. One such candidate is nitric oxide (NO). Thus we performed experiments in the presence of an NO synthase inhibitor. Application of DHPG in the presence of 3-bromo-7-nitro-indazole (5 µM) resulted in a similar decrease in mEPSC frequency to that observed in the absence of inhibitor (frequency decreased to 62 ± 7 % of pre-DHPG; n = 5). No change in mEPSC amplitude was observed (39 ± 8 and 43 ± 10 pA prior to and after application of DHPG).

In conclusion, the effect of DHPG on mEPSC frequency is consistent with a presynaptic locus of expression, but does not exclude other mechanisms such as silencing of synapses.This work was supported by the MRC.

    Fitzjohn, S.M., Kingston, A.E., Lodge, D. & Collingridge, G.L. (1999). Neuropharmacology 38, 1577-1583.

Where applicable, experiments conform with Society ethical requirements.

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