Corticosterone shifts different forms of synaptic potentiation in opposite directions.
Calcium entering the cell via different routes, e.g.,N-methyl-D-aspartate (NMDA) receptors or voltage-dependent calcium channels (VDCCs), plays a pivotal role in hippocampal synaptic potentiation. Since corticosteroid hormones have been reported to enhance calcium influx through VDCCs, one may predict that these hormones facilitate hippocampal synaptic efficacy. Surprisingly, though, stress and corticosteroids have so far been found to reduce synaptic potentiation. Here, we addressed this apparent paradox and examined synaptic potentiation in the CA1 area of hippocampal slices from mice with low basal corticosterone levels 1--4 h after a brief in vitro administration of corticosterone. Nifedipine and APV were used to isolate NMDA receptor-mediated and VDCC-mediated long-term potentiations (LTPs), respectively. We report that corticosterone facilitates synaptic potentiation that depends on activation of VDCCs while impairing synaptic plasticity that is mediated by NMDA receptor activation. The glucocorticoid-receptor (GR) antagonist RU 38486 blocked both the effects of corticosterone. These results indicate that the net effect of corticosteroid hormones on synaptic plasticity is determined by the balance between different types of potentiation, a balance that may be region specific and depends on the experimental conditions. We speculate that these opposite effects on synaptic efficacy are involved in the bidirectional modulation of cognitive performance by corticosteroid hormones.
Krugers
Harm J
HJ
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands. krugers@science.uva.nl
Alfarez
Deborah N
DN
Karst
Henk
H
Parashkouhi
Keyvan
K
van Gemert
Neeltje
N
Joëls
Marian
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009924:Organ Culture Techniques; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D011965:Receptors, Glucocorticoid; D016194:Receptors, N-Methyl-D-Aspartate; D015735:Mifepristone; D003345:Corticosterone