The effects of melatonin on hippocampal physiology

The actions of melatonin on hippocampal evoked-potentials from the CA1 region were studied. Melatonin (0.1–2000μM) caused a concentration-dependent attenuation of the population spike (PS) and excitatory postsynaptic potential (EPSP), however did not influence propagation of the action potential as measured by the fiber volley (FV). Melatonin's actions were biphasic, demonstrating a rapid attenuation followed by a delayed recovery/amplification of the potential. The attenuation of the PS by melatonin (10μM) was significantly reduced by the addition of the MT2 melatonin receptor antagonists 4P-PDOT or luzindole. The actions of melatonin were also regulated by factors including: the time of slice incubation, age of mice and environmental lighting. The reduced binding of melatonin to the hippocampal membranes correlated well with the decreasing responsiveness of hippocampal neurons to melatonin, as the slice age increased. Constitutive activation of MT2 receptors by BMNEP mimicked the attenuation of the PS by melatonin. Addition of the charged melatonin receptor ligand TMEPI caused a delayed (45–60 min) recovery/amplification of the PS. The melatonin-induced depression of the PS could be immediately reversed by application of high frequency stimulation (HFS) commonly used to induce long-term potentiation (LTP). Melatonin was able to convert the inhibition induced by the pairing two pulses with an interstimulus delay of 10–13 ms (paired pulse inhibition—PPI) into facilitation. Melatonin also caused a transient (5 min) conversion of the facilitation caused by the pairing of two pulses with an interstimulus delay of 15–40 ms (paired pulse facilitation—PPF) into inhibition. In conclusion melatonin depressed glutamatergic transmission in the CA1 region of the hippocampus through a receptor-mediated mechanism. These receptor-mediated actions of melatonin may influence learning and memory in the hippocampus. Melatonin as described in this dissertation may act to filter neuronal signals departing from the hippocampus to higher cortical structures.