Corticosteroid effects on calcium signaling in limbic neurons

Abstract

Corticosteroid hormones, which are released in high amounts after stress, easily pass the blood–brain-barrier. In the brain they bind to intracellular receptors which act as transcriptional regulators. These receptors are highly expressed in neurons of the hippocampal formation and the amygdala, areas that play a role in (emotional) memory formation. Voltage gated Ca2+ channels are among the most prominent targets of corticosteroid hormones. When the levels of corticosterone - the prevalent corticosteroid in rats and mice- are low, L-type Ca2+ currents of CA1 hippocampal cells are small. However, when hormone levels rise e.g. after stress, the amplitude of L-type Ca2+ currents will be slowly enhanced, through a process requiring DNA binding of glucocorticoid receptor homodimers. Kinetic properties and voltage dependency of the currents remain unchanged. Neurons in the basolateral amygdala respond in a comparable fashion, but Ca2+ currents of neurons in the dentate gyrus are unaffected by corticosteroids. The stress-induced increase in Ca2+ influx has considerable functional consequences in health and disease. At the short term, i.e. 1–4h after stress, the enhanced Ca2+ influx contributes to stronger firing frequency accommodation and a higher threshold for the induction of long-term potentiation. This helps to normalize neuronal activity after stress and presumably protects earlier encoded, stress-related information. At the longer term, though, increased Ca2+ load may impose a risk, increasing the vulnerability of limbic cells to additional challenges e.g. during epileptic or ischemic episodes.