Corticosteroid Actions in the Hippocampus

Corticosteroid hormones can enter the brain and bind to two intracellular receptor 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 brain predominantly express glucocorticoid receptors, principal cells in limbic structures such as the hippocampus often contain glucocorticoid as well as mineralocorticoid receptors. Recent electrophysiological studies have examined the consequences of transcriptional regulation via the two receptor types for information transfer in the hippocampus. It was found that, under resting conditions, corticosteroids do not markedly alter electrical activity. However, if neurones are shifted towards more depolarized or hyperpolarized potentials due to the action of neurotransmitters, slow and adaptive effects of the corticosteroid hormones become apparent. In general, mineralocorticoid receptor occupation maintains steady electrical activity in hippocampal neurones. Brief activation of glucocorticoid receptors leads to increased influx of calcium, which normally helps to slowly reverse temporarily raised electrical activity. These slow and persistent corticosteroid actions will alter network function within the hippocampus, thus contributing to behavioural adaptation in response to stress. Modulation of hippocampal activity by corticosteroids also affects hippocampal output (e.g. to inhibitory 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 depolarizing inputs, such as those occurring during ischaemia. Similarly, chronically elevated corticosteroid levels (or lack of corticosteroids) could endanger hippocampal cell function. The latter may contribute to the precipitation of clinical symptoms in diseases associated with chronically aberrant corticosteroid levels.