The Journal of Neurophysiology Vol. 78 No. 1 July 1997, pp. 1-9
Copyright ©1997 The American Physiological Society

Glucocorticoid Receptor Activation Lowers the Threshold for NMDA-Receptor-Dependent Homosynaptic Long-Term Depression in the Hippocampus Through Activation of Voltage-Dependent Calcium Channels

Christine M. Coussens^{1, 3}, D. Steven Kerr^{2, 3}, and Wickliffe C. Abraham^{1, 3}

¹ Department of Psychology, ² Department of Pharmacology, and ³ Neuroscience Research Centre, University of Otago, Dunedin, New Zealand

Coussens, Christine M., D. Steven Kerr, and Wickliffe C. Abraham. Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels. J. Neurophysiol. 78: 1-9, 1997. The effects of the glucocorticoid receptor agonist RU-28362 on homosynaptic long-term depression (LTD) were examined in hippocampal slices obtained from adrenal-intact adult male rats. Field excitatory postsynaptic potentials were evoked by stimulation of the Schaffer collateral/commissural pathway and recorded in stratum radiatum of area CA1. Low-frequency stimulation (LFS) was delivered at LTD threshold (2 bouts of 600 pulses, 1 Hz, at baseline stimulation intensity). LFS of the Schaffer collaterals did not produce significant homosynaptic LTD in control slices. However, identical conditioning in the presence of the glucocorticoid receptor agonist RU-28362 (10 µM) produced a robust LTD, which was blocked by the selective glucocorticoid antagonist RU-38486. The LTD induced by glucocorticoid receptor activation was dependent onN-methyl-D-aspartate (NMDA) receptor activity, because the specific NMDA receptor antagonist D()-2-amino-5-phosphonopentanoic acid (D-AP5) blocked the facilitation. However, the facilitation of LTD was not due to a potentiation of the isolated NMDA receptor potential by RU-28362. The facilitation of LTD byRU-28362 was also blocked by coincubation of the L-type voltage-dependent calcium channel (VDCC) antagonist nimodipine. Selective activation of the L-type VDCCs by the agonist Bay K 8644 also facilitated LTD induction. Both nimodipine and D-AP5 were effective in blocking the facilitation of LTD by Bay K 8644. These results indicate that L-type VDCCs can contribute to NMDAreceptor-dependent LTD induction.

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