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 leve ls of plasma corticosterone (CT) in the rat and the levels of cortisol in man. CT is important in maintaining homeostasis and regulating ene rgy production. Homeostasis is maintained by basal activation of the h ippocampal-HPA axis. In response to stress CT secretion is increased. CT activation of receptors in the hippocampus provides feedback inhibi tion of the HPA axis to return the system to basal activity. There are two types of CT receptors: the mineralocorticoid receptor (MR) and th e glucocorticoid receptor (GR). CT has a 10-fold higher affinity for M R than GR. Normal basal levels of CT occupy the majority of the MR. Du ring the diurnal surge of CT and following the presentation of a stres sful stimulus, the MR and GR are both maximally occupied. To begin to understand how CT influences the hippocampal-HPA axis, intracellular r ecording techniques in the hippocampal brain slice preparation were us ed to determine how high concentrations of CT may alter cell character istics 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 norma l rat in the morning. Acute administration of 100 nM CT decreased acti on 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 pote ntials (EPSP) or inhibitory postsynaptic potentials (IPSP) declined in cells recorded from ADX animals and ADX rats acutely treated with hig h concentrations of CT (ADX/CT). The EPSPs and IPSPs were stable in ce lls from ADX + CT rats exposed to high CT concentrations. We conclude from these data that chronic CT treatment is necessary to maintain EPS P and IPSP amplitude. Also, acute administration of a high concentrati on of CT alters the output of the CA1 hippocampal pyramidal cells by i ncreasing the number of action potentials elicited by a depolarizing c urrent pulse but does not alter the amplitude of subthreshold EPSPs an d IPSPs. (C) 1995 Wiley-Liss, Inc.