Selective modulation of Ca(2+) 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 Ca(2+) 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 Ca(2+) channels. 1 microM of 5-HT inhibited homosynaptic LTD induced by low frequency stimulation. This effect of 5-HT could be blocked by the selective 5-HT(1A) 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 LTP 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 properties in the brain.
Normann
Claus
C
Department of Psychiatry, University of Freiburg, Hauptstr. 5, D-79104 Freiburg, Germany. claus_normann@psyallg.ukl.uni-freiburg.de
Clark
Kristin
K
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D010879:Piperazines; D011725:Pyridines; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium