Potentiation phase of spike timing-dependent neuromodulation by a serotonergic interneuron involves an increase in the fraction of transmitter release.
In the mollusk, Tritonia diomedea, the serotonergic dorsal swim interneuron (DSI) produces spike timing-dependent neuromodulation (STDN) of the synaptic output of ventral swim interneuron B (VSI) resulting in a biphasic, bidirectional change of synaptic strength characterized by a rapid heterosynaptic potentiation followed by a more prolonged heterosynaptic depression. This study examined the mechanism underlying the potentiation phase of STDN. In the presence of 4-aminopyridine, which blocks the depression phase and enhances transmitter release from VSI, rapidly stimulating VSI led to a steady-state level of transmitter depletion during which potentiation by DSI or serotonin (5-HT) was eliminated. Cumulative plots of excitatory postsynaptic currents were used to estimate changes in the size and replenishment rate of the readily releasable pool (RRP) and the fraction of release. 5-HT application increased transmitter release without altering replenishment rate. The magnitude of 5-HT-evoked potentiation correlated with the increase in the fraction of release. A phenomenological model of the synapse further supported the hypothesis that 5-HT-induced potentiation was caused by an increase in the fraction of release and correctly predicted no change in frequency facilitation. A dynamic version of the model correctly predicted the effect of DSI stimulation under a variety of conditions. Finally, depletion of internal Ca(2+) stores with cyclopiazonic acid showed that Ca(2+) from internal stores is necessary for the 5-HT-induced potentiation. The data indicate that 5-HT released from DSI increases the fraction of the RRP discharged during VSI action potentials using a mechanism that involves Ca(2+) extrusion from internal stores, resulting in time- and state-dependent neuromodulation.
Sakurai
Akira
A
Department of Biology, Georgia State University, Atlanta, GA 30302-4010, USA. akira@gsu.edu
Calin-Jageman
Robert J
RJ
Katz
Paul S
PS
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D003116:Color; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D008839:Microelectrodes; D018377:Neurotransmitter Agents / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D049871:Tritonia Sea Slug / Q000502:physiology*
D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D012701:Serotonin; D015761:4-Aminopyridine