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.
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