Effects of mineralocorticoid and glucocorticoid receptors on long-term potentiation in the CA3 hippocampal field

Abstract

We have previously shown that the two types of adrenal steroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) produce opposite effects on long-term potentiation (LTP) in the dentate gyrus (in vivo) and CA1 hippocampal field (in vitro). More specifically, MR activation enhanced and prolonged LTP, whereas GR activation suppressed LTP in these areas and also produced a long-term depression (LTD) of the synaptic response. In the present experiment we investigated acute effects of MR and GR activation on LTP induction in the mossy fiber and commissural/associational input to the CA3 hippocampal field, since the mechanisms underlying LTP induction in these two pathways differ, the former being N-methyl- d-aspartate receptor (NMDA R) independent while the latter being NMDA R-dependent. Rats were either adrenalectomized (ADX) or adrenally intact. ADX animals were acutely injected with either the specific MR agonist, aldosterone, the specific GR agonist RU 28362 or vehicle. One hour following the injection, the animals were prepared for electrophysiological recording/stimulation. Field potential recordings were performed in the radiatum or laconosum/moleculare layers of the CA3 field, with stimulation of either the mossy fibers or the commissural/associational input (from the contralateral hemisphere). We also replicated our previous findings by recording in the dentate gyrus with stimulation of the medial perforant pathway, in the same animals. As observed in our previous study in the dentate gyrus, we found an enhancement and a suppression of LTP with MR and GR activation, respectively. Similarly, for the commissural/associational input to CA3, MR activation enhanced LTP, while GR activation reduced it. In contrast, for the mossy fiber input to CA3, neither MR nor GR activation significantly affected LTP induction. These results indicate that adrenal steroids may modulate LTP induction in the hippocampus via an interaction with glutamatergic NMDA R.