Melatonin inhibits hippocampal long-term potentiation
Department of Neurobiology; Weaver Lab
Medical Subject Headings
Animals; Antioxidants; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Electric Stimulation; Excitatory Postsynaptic Potentials; Hippocampus; Isoquinolines; Long-Term Potentiation; Male; Melatonin; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Kinase Inhibitors; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Sulfonamides; Synaptic Transmission; Tryptamines
Neuroscience and Neurobiology
The goal of this study is to investigate the effect of the hormone melatonin on long-term potentiation and excitability measured by stimulating the Schaffer collaterals and recording the field excitatory postsynaptic potential from the CA1 dendritic layer in hippocampal brain slices from mice. Application of melatonin produced a concentration-dependent inhibition of the induction of long-term potentiation, with a concentration of 100 nm producing an approximately 50% inhibition of long-term potentiation magnitude. Long-duration melatonin treatments of 6 h were also effective at reducing the magnitude of long-term potentiation. Melatonin (100 nm) did not alter baseline evoked responses or paired-pulse facilitation recorded at this synapse. The inhibitory actions of melatonin were prevented by application of the melatonin (MT) receptor antagonist luzindole as well as the MT2 receptor subtype antagonist 4-phenyl-2-propionamidotetraline. These inhibitory actions of melatonin were lost in mice deficient in MT2 receptors but not those deficient in MT1 receptors. In addition, application of the protein kinase A inhibitor H-89 both mimicked the effects of melatonin and precluded further inhibition by melatonin. Finally, the application an activator of adenylyl cyclase, forskolin, overcame the inhibitory effects of melatonin on LTP without affecting the induction of long-term potentiation on its own. These results suggest that hippocampal synaptic plasticity may be constrained by melatonin through a mechanism involving MT2-receptor-mediated regulation of the adenylyl cyclase-protein kinase A pathway.
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Citation: Eur J Neurosci. 2005 Nov;22(9):2231-7. Link to article on publisher's site
Wang, Louisa M.; Suthana, Nanthia A.; Chaudhury, Dipesh; Weaver, David R.; and Colwell, Christopher S., "Melatonin inhibits hippocampal long-term potentiation" (2005). Neurobiology Publications and Presentations. Paper 69.