title: Long-term changes in excitability induced by protein kinase C activation in Aplysia sensory neurons.
abstract: 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. Although 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 4beta-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 (3 h) after treatment was independent of protein synthesis, while it was disrupted at the long-term (24 h) 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.
authors.affiliation: Département de Physiologie, Laboratoire de Neurobiologie et Comportement, Institut de Recherches Cliniques de Montréal and Centre de Recherches en Sciences Neurologiques, Université de Montréal, Succursale Centre-ville, H3C 3J7 Quebec, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Manseau
authors.forename: W S
authors.initials: WS
authors.lastname: Sossin
authors.forename: V F
authors.initials: VF
authors.lastname: Castellucci
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001048:Aplysia; D002478:Cells, Cultured; D004789:Enzyme Activation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D017952:Ganglia, Invertebrate / Q000502:physiology*; D008959:Models, Neurological; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C