Diurnal Differences and Adrenal Involvement in Calmodulin Stimulation of Hippocampal Adenylate Cyclase Activity

Abstract

Calclum/calmodulin-dependent processes a r e altered by manipulations of the hypothalamic-pituitary-adrenal axis, and a r e associated 'with changes in synaptic efficacy in t h e hippocampus, s u c h as long-term potentiation. Recent evidence indicates that there are tliurnal variations in t h e threshold for long-term potentiation, as well as diverse effects of the adrenals and of adrenal steroids on e:octrical activity related to long-term potentiation. In order to probe possible mechanisms underlying these observations, we inve::tigated the effects of the diurnal cycle, as well as adrenalectomy (ADX) and adrenal demedullation on adenylate cyclase activ::y. In hippocampal, but not cortical, membranes the adenylate cyclase response.to calmodulin w a s higher during the beginning of thi: dark phase of the cycle, when endogenous corticosterone levels a r e high. Basal and forskolin-stimulated adenylate cyclase activity did not exhibit diurnal variation in either brain region. ADX (6 and 14 days) depressed the adenylate cyclase response to calni<)dulin in hippocampal membranes, and abolished the diurnal difference. ADX had smaller effects on this response in cortical menibranes. ADX also attenuated basal and forskolin-stimulated adenylate cyclase activity, but these changes were less striking than effects on calmodulin-stimulated activity. Demedullation (14 days), generating corticosterone levels in the low physiological ran:;!?, mirrored the effects of ADX on hippocampal adenylate cyclase activity. Corticosterone (20 to 25 pghnl in the drinking water) did riot consistently prevent ADX effects on adenylate cyclase activity. These results demonstrate that adrenal effects on adenylate -e activity a r e regionally spectfic within the brain, and they suggest that other adrenal secretions besides glucocorticoids ma) b e involved in the feedback of the diurnal rhythm on the hippocampus. Taken together with our recent finding that chronic stre -3 or corticosterone injection selectively attenuated the adenylate cyclase response to calmodulin in cortical, but not hippocampal inembranes our findings provide further support for a role of the pituitary-adrenal axis in modulating neural calmodulindep,:ndent adenylate cyclase activity.Out interest in neurochemical and hormonal factors involved in neu1.d processes underlying cognitive function has led us to expi:m the biochemical differences between the active waking stat', and the sleep state of the rat. We were prompted to initiate thex studies by anecdotal observations on the phenomenon of jet !;ig and by studies which showed that the electrical activity of the llippocampus shows a diurnal variation (1-3), with an increase in !lie electrical field potential of the dentate gyrus during the actliity phase of the diurnal cyclc of rats and squirrel monkeys(1) l h a and Martinez (2) found an adrcnal influence on synaptic efhcy in the dentate gyrus, such that intact rats experienccd the W i h synaptic efficacy during their waking phase while adrenalectoinired (ADX) rats sho...