LONG-TERM AND SHORT-TERM ADMINISTRATION OF CORTICOSTERONE ALTERS CA1 HIPPOCAMPAL NEURONAL PROPERTIES

The hippocampus contains a high concentration of the two corticosterone (CT) receptor subtypes, i.e. the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The endogenous steroid hormone CT has tenfold higher affinity for the MR than the GR. Under physiological conditions the MR is 80-95% occupied; during the daily diurnal surge of CT and following a stressful stimulus, the MR is 100% occupied and the GR 67-80% occupied. Previous studies have shown that CT can alter the synthesis of proteins within 30 min whereas it takes up to 7 days to alter the synthesis of other proteins. The physiological relevance of MR and GR activation is not totally understood. Intracellular recording techniques in hippocampal slices maintained in vitro were used to investigate chronic continuous or short-term effects of CT administration on hippocampal pyramidal cell activity. Rats were adrenalectomized (ADX) with or without CT replacement. The CT pellet used provided continuous plasma corticosterone levels equal to that seen in a normal rat in the morning. On the day of the experiment, slices from ADX animals were perfused with buffer containing no steroid, 1 nM CT or the selective GR agonist RU28362. Slices taken from ADX with CT pellet treated rats were superfused with buffer containing 1 nM CT or no steroid. Short-term and chronic CT treatment increased the membrane time constant, decreased the slow afterhyperpolarization (sAHP) amplitude, and increased the number of action potentials elicited by a depolarizing current pulse. Chronic continuous CT treatment decreased input resistance measured at 300 ms, increased action potential amplitude and duration, and decreased the fast afterhyperpolarization (fAHP) amplitude. The net result of these actions would be to increase pyramidal cell excitability, i.e. increase the probability of action potential generation and action potential firing frequency, and to increase the synaptic output of the CA1 pyramidal cell to its efferent connections. We conclude that chronic continuous low CT concentrations, equal to those plasma concentrations normally present throughout the day, modulate the physiology of the CA1 hippocampal pyramidal cell.