Steroids and electrical activity in the brain.
Corticosteroid hormones can enter the brain and bind to two receptor subtypes: the high affinity mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) with approximately 10-fold lower affinity. Under physiological conditions the degree of receptor occupation will range from a predominant MR occupation (at the beginning of the inactive period, under rest) to concurrent activation of MRs and GRs (at the circadian peak and after stress). With in vitro electrophysiological recording techniques we observed that neuronal excitability in the CA1 hippocampal field is under a long-term control of MR- and GR-mediated events. The predominant occupation of MRs is associated with a stable amino acid-carried synaptic transmission; calcium- and potassium-currents are small, as are the responses to biogenic amines. Occupation of GRs in addition to MRs results in a gradual failure of CA1 neurons to respond to repeated stimulation of amino acid-mediated input; ionic conductances and responses to biogenic amines are large. In general, electrical properties recorded when both MRs and GRs are unoccupied (i.e. after adrenalectomy) resemble the responses observed when both receptor types are activated. The corticosterone dependency of electrical properties is thus U-shaped. We conclude that MR occupation may be responsible for the maintenance of information processing in the CA1 field and the stability of the circuit. Additional activation of GRs will initially suppress synaptic activity, but may eventually result in an increased instability and even vulnerability of the neuronal networks.
Joëls
M
M
Department of Experimental Zoology, University of Amsterdam, The Netherlands.
Hesen
W
W
Karst
H
H
de Kloet
E R
ER
D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D008564:Membrane Potentials; D011965:Receptors, Glucocorticoid / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid