Potentiation of synaptic transmission by (S)-3,5-dihydroxy phenylglycine in the rat dentate gyrus in vitro: A role for voltage dependant calcium channels and protein kinase C

Abstract

1. 1. The authors have previously shown that direct activation of metabotropic glutamate receptors (mGluRs) by (S)-3,5-dihydroxyphenylglycine ((S)-DHPG) can induce a long-lasting potentiation of synaptic transmission in the rat dentate gyrus in vitro. Here the authors provide further characterisation of this agonist-induced potentiation. 2. 2. Field excitatory post-synaptic potentials were recorded from the dentate gyrus of rat hippocampal slices prepared by standard methods. 3. 3. (S)-DHPG (40 μM) induced a significant potentiation of the field EPSP slope (148. 6 ± 4. 3% compared to controls, n = 5), which occluded tetanically-induced LTP. 4. 4. This potentiation was inhibited by the PKC inhibitors staurosporine (0. 1 μM) and H-7 (100 μM) and by the voltage dependent Ca 2+ channel (VDCC) blockers NiCl 2 (50 μM) and nifedipine (20 μM). 5. 5. The mGluR5 specific agonist (RS)-2-Chloro-5-Hydroxyphenylglycine (CHPG) did not induce a potentiation when applied to slices at concentrations from 20 μM to 1 mM indicating that the (S)-DHPG potentiation may be mediated through group I subtype 1 mGluRs. 6. 6. In conclusion the (S)-DHPG-induced potentiation observed in our studies may be PKC dependent and is likely to be mediated through both T/L subtype VDCC and mGluR1 subtype receptors.