title: 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 Ca(2+) 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 Ca(2+) currents of CA1 hippocampal cells are small. However, when hormone levels rise e.g. after stress, the amplitude of L-type Ca(2+) 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 Ca(2+) currents of neurons in the dentate gyrus are unaffected by corticosteroids. The stress-induced increase in Ca(2+) influx has considerable functional consequences in health and disease. At the short term, i.e. 1-4h after stress, the enhanced Ca(2+) 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 Ca(2+) load may impose a risk, increasing the vulnerability of limbic cells to additional challenges e.g. during epileptic or ischemic episodes.
authors.affiliation: Department of Neuroscience and Pharmacology, Division of Neuroscience, Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands. m.joels@umcutrecht.nl
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
authors.forename: Henk
authors.initials: H
authors.lastname: Karst
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D008032:Limbic System / Q000502:physiology*; D017774:Long-Term Potentiation; D051379:Mice; D009431:Neural Conduction; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000305:Adrenal Cortex Hormones; D015220:Calcium Channels; D011965:Receptors, Glucocorticoid