LONG-TERM CHANGES IN EXCITABILITY INDUCED BY PROTEIN KINASE C ACTIVATION IN
APLYSIA SENSORY NEURONS.
Frederic Manseau, Wayne S. Sossin and Vincent F. Castellucci.
Laboratoire de Neurobiologie et comportement, Institut de Recherches
Cliniques de Montreal and Centre de Recherches en Sciences Neurologiques,
Departement de physiologie, Université de Montréal, Canada. Department of
Neurology, Montreal Neurological Institute, McGill University, Canada.
APStracts 4:353N, 1997.
Protein kinases A (PKA) and C (PKC) play a central role as intracellular
transducers during simple forms of learning in Aplysia. These two proteins
seem to cooperate in mediating the different forms of plasticity underlying
behavioral modifications of defensive reflexes in a state- and time-dependent
manner. While short- and long-term changes in the synaptic efficacy of the
connections between mechanosensory neurons and motoneurons of the reflex have
been well characterized, there is also a distinct intermediate phase of
plasticity that is not as well understood. Biochemical and physiological
experiments have suggested a role for PKC in the induction and expression of
this form of facilitation. In this report, we demonstrate that PKC activation
can induce both intermediate- and long-term changes in the excitability of
sensory neurons (SNs). Short application of 4(-Phorbol ester 12,13-dibutyrate
(PDBU), a potent activator of PKC, produced a long lasting increase in the
number of spikes fired by SNs in response to depolarizing current pulses. This
effect was observed in isolated cell culture and in the intact ganglion; it
was blocked by a selective PKC inhibitor (Chelerythrine). Interestingly, the
increase in excitability measured at an intermediate-term time point (3h)
after treatment was independent of protein synthesis, while it was disrupted
at the long-term (24h) time point by the general protein synthesis inhibitor,
anisomycin. In addition to suggesting that PKC as well as PKA are involved in
long lasting excitability changes, these findings support the idea that memory
formation involves multiple stages that are mechanistically distinct at the
Received 10 July 1997; accepted in final form 1 December 1997.
APS Manuscript Number J574-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997