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J Neurophysiol 98: 1975-1987, 2007. First published August 8, 2007; doi:10.1152/jn.00702.2007
0022-3077/07 $8.00
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Potentiation Phase of Spike Timing-Dependent Neuromodulation by a Serotonergic Interneuron Involves an Increase in the Fraction of Transmitter Release

Akira Sakurai*, Robert J. Calin-Jageman* and Paul S. Katz

Department of Biology, Georgia State University, Atlanta, Georgia

Submitted 25 June 2007; accepted in final form 5 August 2007

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 Ca2+ stores with cyclopiazonic acid showed that Ca2+ 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 Ca2+ extrusion from internal stores, resulting in time- and state-dependent neuromodulation.


Address for reprint requests and other correspondence: A. Sakurai, Dept. of Biology, Georgia State University, P.O. Box 4010, Atlanta, GA 30302-4010 (E-mail: akira{at}gsu.edu)




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A. Sakurai and P. S. Katz
State-, Timing-, and Pattern-Dependent Neuromodulation of Synaptic Strength by a Serotonergic Interneuron
J. Neurosci., January 7, 2009; 29(1): 268 - 279.
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E. S. Hill, A. Sakurai, and P. S. Katz
Transient Enhancement of Spike-Evoked Calcium Signaling by a Serotonergic Interneuron
J Neurophysiol, November 1, 2008; 100(5): 2919 - 2928.
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