Differential Effects of 4-Aminopyridine, Serotonin, and Phorbol Esters on Facilitation of Sensorimotor Connections in Aplysia. Sugita, Shuzo, Douglas A. Baxter and John H. Byrne. Laboratory of origin: Department of Neurobiology and Anatomy, University of Texas Medical School-Houston, P.O. Box 20708, Houston, TX 77225, U.S.A..
APStracts 3:0229N, 1996.
ABSTRACT
Serotonergic modulation of sensory neurons in Aplysia and their synaptic connections with follower cells has been used extensively as a model system with which to study mechanisms underlying neuronal plasticity. Serotonin (5- HT)-induced facilitation of sensorimotor connections is due to at least two processes: a process related to the broadening of presynaptic action potentials and a spike duration-independent (SDI) process that may involve mobilization of transmitter. We have examined the relationship between spike broadening and synaptic facilitation of relatively nondepressed sensorimotor connections in the intact pleural-pedal ganglia. Previously, 5-HT-induced spike broadening in the sensory neuron was shown to be primarily due to the modulation of a voltage-dependent K+ current (IK,V). Low concentrations (20 - 30 ? [mu] M) of 4-aminopyridine (4- AP) were used to rather selectively block IK,V. 4-AP increased spike duration in the sensory neuron and the excitatory postsynaptic potential (EPSP) in the motor neuron. The temporal development of 4- AP-induced spike broadening closely paralleled that of synaptic facilitation. Thus, spike broadening via the reduction of IK,V can directly contribute to synaptic facilitation. The relationship between 5- HT (10 ? [mu] M)-induced spike broadening and enhancement of the EPSP was also analyzed. We found that components of 5-HT-induced synaptic facilitation preceded the development of 5-HT-induced spike broadening. The comparison between the results of 4-AP and 5-HT revealed that the SDI processes made an important contribution to the rapid development of 5-HT-induced synaptic facilitation and that spike broadening made an important contribution to its maintenance. The SDI process and a slowly developing component of 5-HT-induced spike broadening are mediated, at least in part, by the activation of protein kinase C (PKC). Application of phorbol 12, 13-diacetate (PDAc), an activator of PKC, partially mimicked the effects of 5-HT on spike duration and the EPSP. PDAc- induced enhancement of the EPSP preceded the slower development of PDAc- induced spike broadening. Like 5-HT, PDAc enhanced the EPSP via both spike broadening and the SDI processes. In addition, a 15-min exposure to PDAc occluded 5- HT-induced enhancement of the EPSP, suggesting that PKC and 5-HT engage similar or overlapping mechanisms. Based on these results, and others, we propose a time-dependent hypothesis for the 5-HT-induced synaptic facilitation of nondepressed synapses, in which multiple second messenger/protein kinase systems mediate the actions of 5-HT via both spike duration-dependent and independent processes. 

Received 26 December 1995; accepted in final form  4 September 1996.
APS Manuscript Number J863-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996