Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice

The pineal product melatonin that acts on specific melatonin receptors has been implicated in pathobiological mechanisms of neuropsychiatric disorders including Alzheimer's disease. We used mice lacking melatonin MT2 receptors (MT2 knockouts) to investigate the role of these receptors in synaptic plasticity and learning-dependent behavior. In field CA1 of hippocampal slices from wild-type mice, theta burst stimulation induced robust and stable long-term potentiation that was smaller and decremental in slices from MT2 knockouts. Tested in an elevated plus-maze on two consecutive days, wild-type mice showed shorter transfer latencies to enter a closed arm on the second day; this experience-dependent behavior did not occur in MT2 knockouts. These results suggest that MT2 receptors participate in hippocampal synaptic plasticity and in memory processes.