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  • Title: Presynaptic depression of inhibitory postsynaptic potentials by metabotropic glutamate receptors in rat hippocampal CA1 pyramidal cells.
    Author: Jouvenceau A, Dutar P, Billard JM.
    Journal: Eur J Pharmacol; 1995 Aug 04; 281(2):131-9. PubMed ID: 7589200.
    Abstract:
    The effects of the metabotropic glutamate (mGlu) receptor agonists (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or 1S,3R-ACPD on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic responses have been investigated in vitro in CA1 pyramidal cells of rat hippocampal slices. Bath application of both agonists depolarized the resting membrane potential and increased membrane resistance. Simultaneously, the afterhyperpolarization induced by a burst of spikes as well as spike accomodation were blocked. Stimulation of the stratum radiatum induced in CA1 pyramidal cells an early excitatory postsynaptic potential (EPSP) followed by a fast GABAA and a slow GABAB-mediated inhibitory postsynaptic potentials (IPSPs). All synaptic responses were dose dependently depressed by mGlu receptor agonists. At low concentration, (+/-)-trans-ACPD (10-100 microM) and 1S,3R-ACPD (10 microM) consistently reduced the EPSP, slightly depressed the fast IPSP but greatly decreased the slow IPSP. Increasing the concentration of mGlu receptor agonists to 200 microM and 50 microM, respectively further depressed the EPSP and dramatically reduced the amplitude of both IPSPs. In the presence of the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D-(-)-2-amino-5-phosphonovaleric acid (30 microM), monosynaptically evoked IPSPs were still depressed by mGlu receptor agonists. In the same conditions, the discharge frequency of spontaneous IPSPs which reflect the activity of GABAergic interneurons was enhanced by low doses of mGlu receptor agonists but depressed with higher concentrations. On the other hand, the postsynaptic hyperpolarization and decrease in membrane resistance induced by the GABAB receptor agonist baclofen applied in the bath or by microiontophoresis were not affected by mGlu receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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