title: Cholinergic Responsiveness of Rat CA1 Hippocampal Neurons In Vitro: Modulation by Corticosterone and Stress.
abstract: Corticosterone can activate two corticosteroid receptor types in rat hippocampus: low doses activate mineralocorticoid receptors (MR) while high doses additionally activate glucocorticoid receptors (GR). We found that corticosterone, administered to adrenalectomized rats in vivo, dose-dependently modulates carbachol responsiveness of CA1 hippocampal neurons, recorded subsequently in vitro. Thus, the carbachol (3 µM) induced membrane depolarization in CA1 neurons was relatively large in hippocampal slices where either (almost) no corticosteroid receptors were activated (0-1 µg corticosterone/100g body weight) or where both MRs and GRs were occupied by high corticosterone doses (100-1000 µg/100g). Slices from rats that received intermediate doses of corticosterone (10-30 µg/100g) resulting in predominant MR occupation, displayed significantly suppressed carbachol responses. In adrenally intact rats with MRs and GRs fully activated by a very high dose of corticosterone (1 mg/100g), carbachol responses were increased compared to rats that received only the vehicle or that were untreated. When endogenous corticosterone levels were elevated by ether stress, carbachol responses were not increased. These findings suggest that a shift in the relative occupation of MRs and GRs occurring under physiological conditions is associated with modulation of acetylcholine sensitivity in CA1 neurons. After stress, however, the sensitivity to acetylcholine is rather low, although MRs and GRs are fully activated by endogenous corticosterone; this may point to the involvement of additional stress-induced factors modulating the cholinergic responses.
authors.affiliation: Graduate School for Neurosciences, Institute for Neurobiology, University of Amsterdam, Department Experimental Zoology, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
authors.initials: W
authors.lastname: Hesen
authors.initials: M
authors.lastname: Joëls