Serotonin controls the magnitude of LTP induced by theta bursts via an action on NMDA-receptor-mediated responses.

The present studies examined the inhibitory effects of serotonin (5-HT) on LTP in the context of the theta burst stimulation paradigm and its known relationship to the induction chemistries of LTP. Comparisons were made between the effects of various dosages of 5-HT on: (i) the extent to which the second member of a pair of theta bursts was facilitated over the first member of the pair; and (ii) the degree of LTP produced by the paired bursts. Both LTP and burst facilitation were affected in a graded manner by the drug: at high concentrations LTP was completely blocked and burst enhancement was minimal, at lower dosages LTP stabilized at a reduced level while burst responses showed substantial but still impaired facilitation. The competitive antagonist AP-5 was then used to test if 5-HT blocked the NMDA receptor mediated synaptic currents which normally occur during the facilitated burst responses. AP-5 had no effect on the size of burst responses in slices pre-treated with 5-HT indicating that serotonin suppressed the activation of the NMDA receptors by theta stimulation. Serotonin depressed the facilitation of burst responses in slices pre-treated with AP-5 indicating that it also reduces the enhanced AMPA receptor mediated currents that occur during theta pattern stimulation. These results are discussed in terms of the known effects of serotonin on hippocampal physiology and how these might interact with the machinery whereby theta stimulation activates NMDA receptor mediated currents.