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 it s known relationship to the induction chemistries of LTP. Comparisons were made between the effects of various dosages of 5-HT on: (i) the e xtent to which the second member of a pair of theta bursts was facilit ated over the first member of the pair; and (ii) the degree of LTP pro duced by the paired bursts. Both LTP and burst facilitation were affec ted in a graded manner by the drug: at high concentrations LTP was com pletely blocked and burst enhancement was minimal, at lower dosages LT P stabilized at a reduced level while burst responses showed substanti al but still impaired facilitation. The competitive antagonist AP-5 wa s then used to test if 5-HT blocked the NMDA receptor mediated synapti c currents which normally occur during the facilitated burst responses . AP-5 had no effect on the size of burst responses in slices pre-trea ted with 5-HT indicating that serotonin suppressed the activation of t he NMDA receptors by theta stimulation. Serotonin depressed the facili tation of burst responses in slices pre-treated with AP-5 indicating t hat 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.