Corticosteroid actions in the hippocampus

Corticosteroid hormones can enter the brain and bind to two intracellular r eceptor types that regulate transcription of responsive genes: (i) the high affinity mineralocorticoid receptors and (ii) the glucocorticoid receptors with approximately 10-fold lower affinity. Although most cells in the brai n predominantly express glucocorticoid receptors, principal cells; in limbi c structures such as the hippocampus often contain glucocorticoid as well a s mineralocorticoid receptors. Recent electrophysiological studies have exa mined the consequences of transcriptional regulation via the two receptor t ypes for information transfer in the hippocampus. It was found that, under resting conditions, corticosteroids do not markedly alter electrical activi ty. However, if neurones are shifted towards more depolarized or hyperpolar ized potentials due to the action of neurotransmitters, slow and adaptive e ffects of the corticosteroid hormones become apparent. In general, mineralo corticoid receptor occupation maintains steady electrical activity in hippo campal neurones. Brief activation of glucocorticoid receptors leads to incr eased influx of calcium, which normally helps to slowly reverse temporarily raised electrical activity. These slow and persistent corticosteroid actio ns will alter network function within the hippocampus, thus contributing to behavioural adaptation in response to stress. Modulation of hippocampal ac tivity by corticosteroids also affects hippocampal output (e.g. to inhibito ry interneurones which control hypothalamic-pituitary-adrenal axis activity ). The enhanced calcium influx after glucocorticoid receptor activation can become a risk factor when cells are simultaneously exposed to strong depol arizing inputs, such as those occuring during ischaemia. Similarly, chronic ally elevated corticosteroid levels (or lack of corticosteroids) could enda nger hippocampal cell function. The latter may contribute to the precipitat ion of clinical symptoms in diseases associated with chronically aberrant c orticosteroid levels.