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 biochemical level.

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