CHRONIC CORTICOSTERONE TREATMENT MAINTAINS SYNAPTIC ACTIVITY OF CA1 HIPPOCAMPAL PYRAMIDAL CELLS - ACUTE HIGH CORTICOSTERONE ADMINISTRATION INCREASES ACTION-POTENTIAL NUMBER

The hypothalamic-pituitary-adrenocortical (HPA) axis controls the levels of plasma corticosterone (CT) in the rat and the levels of cortisol in man. CT is important in maintaining homeostasis and regulating energy production. Homeostasis is maintained by basal activation of the hippocampal-HPA axis. In response to stress CT secretion is increased. CT activation of receptors in the hippocampus provides feedback inhibition of the HPA axis to return the system to basal activity. There are two types of CT receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). CT has a 10-fold higher affinity for MR than GR. Normal basal levels of CT occupy the majority of the MR. During the diurnal surge of CT and following the presentation of a stressful stimulus, the MR and GR are both maximally occupied. To begin to understand how CT influences the hippocampal-HPA axis, intracellular recording techniques in the hippocampal brain slice preparation were used to determine how high concentrations of CT may alter cell characteristics and/or evoked synaptic activity. Two treatment groups were used, i.e., adrenalectomized (ADX) and ADX with CT pellet replacement (ADX + CT) that produced plasma blood levels equal to that seen in a normal rat in the morning. Acute administration of 100 nM CT decreased action potential threshold and the number of action potentials elicited by a depolarizing current pulse in cells from both the ADX and ADX + CT treated rats. The amplitude of the evoked excitatory postsynaptic potentials (EPSP) or inhibitory postsynaptic potentials (IPSP) declined in cells recorded from ADX animals and ADX rats acutely treated with high concentrations of CT (ADX/CT). The EPSPs and IPSPs were stable in cells from ADX + CT rats exposed to high CT concentrations. We conclude from these data that chronic CT treatment is necessary to maintain EPSP and IPSP amplitude. Also, acute administration of a high concentration of CT alters the output of the CA1 hippocampal pyramidal cells by increasing the number of action potentials elicited by a depolarizing current pulse but does not alter the amplitude of subthreshold EPSPs and IPSPs. (C) 1995 Wiley-Liss, Inc.