Melatonin inhibits hippocampal long-term potentiation

Louisa M. Wang, Nanthia A. Suthana, Dipesh Chaudhury, David R. Weaver, Christopher S. Colwell

Research output: Contribution to journalArticle

Abstract

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 ≈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.

Original languageEnglish (US)
Pages (from-to)2231-2237
Number of pages7
JournalEuropean Journal of Neuroscience
Volume22
Issue number9
DOIs
StatePublished - Nov 1 2005

Fingerprint

Long-Term Potentiation
Melatonin
Melatonin MT2 Receptor
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Melatonin MT1 Receptor
Melatonin Receptors
Neuronal Plasticity
Excitatory Postsynaptic Potentials
Colforsin
Protein Kinase Inhibitors
Synapses
Hippocampus
Hormones

Keywords

  • Hippocampus
  • LTP
  • Melatonin
  • Mice
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Melatonin inhibits hippocampal long-term potentiation. / Wang, Louisa M.; Suthana, Nanthia A.; Chaudhury, Dipesh; Weaver, David R.; Colwell, Christopher S.

In: European Journal of Neuroscience, Vol. 22, No. 9, 01.11.2005, p. 2231-2237.

Research output: Contribution to journalArticle

Wang, Louisa M. ; Suthana, Nanthia A. ; Chaudhury, Dipesh ; Weaver, David R. ; Colwell, Christopher S. / Melatonin inhibits hippocampal long-term potentiation. In: European Journal of Neuroscience. 2005 ; Vol. 22, No. 9. pp. 2231-2237.
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