Selective modulation of Ca2+ influx pathways by 5-HT regulates synaptic long-term plasticity in the hippocampus

Both long-term potentiation (LTP) and long-term depression (LTD) can be induced in the Schaffer collateral-CA1 synapse of the hippocampus either by repetitive stimulation of afferent fibres with the frequency of the stimulation determining the polarity of the response ;or by associative pairing of pre- and postsynaptic activity. An increase in postsynaptic intracellular Ca2+ concentration is an important signal for the induction of long-term synaptic plasticity. In patch-clamp experiments on hippocampal brain slices, we tested the modulation of different forms of synaptic plasticity by the neurotransmitter serotonin (5-HT) which is known to inhibit high-voltage activated Ca2+ channels. 1 mu M of 5-HT inhibited homosynaptic LTD induced by low frequency stimulation. This effect of 5-HT could be blocked by the selective 5-HT1A antagonist WAY 100635. Low frequency-induced LTD is both dependent on Ca (2+) influx through NMDA receptors and high-voltage activated Ca (2+) channels. It was blocked by the NMDA-receptor antagonist D-AP5 and by the N-type Ca (2+) channel antagonist omega-conotoxin GIVA. Tetanus induced UP was not affected by low concentrations of 5-HT, whereas depotentiation of LTP by asynchronous pairing of EPSPs and postsynaptic action potentials was completely abolished with 5-HT in the bath solution. We conclude that those forms of plasticity which depend on Ca (2+) influx via high-voltage activated Ca (2+) channels are subject to modulation by 5-HT. This might be a relevant mechanism by which 5-HT modifies basic network proper-ties in the brain. (c) 2005 Elsevier B.V All rights reserved.