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The Journal of Neuroscience, February 15, 2001, 21(4):1247-1256

Ca²⁺-Independent Protein Kinase C Apl II Mediates the Serotonin-Induced Facilitation at Depressed Aplysia Sensorimotor Synapses

Frédéric Manseau¹, Xiaotang Fan², Tina Hueftlein², Wayne S. Sossin², and Vincent F. Castellucci¹

¹ Laboratoire de Neurobiologie et Comportement, Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Montréal, Canada H3C 3J7, and ² Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Canada H3A 2B4

At nondepressed Aplysia sensory to motor synapses, serotonin (5-HT) facilitates transmitter release primarily through a protein kinase A pathway. In contrast, at depressed Aplysia sensory to motor synapses, 5-HT facilitates transmitter release primarily through a protein kinase C (PKC)-dependent pathway. It is known that only two phorbol ester-activated PKC isoforms, the Ca²⁺-dependent PKC Apl I and the Ca²⁺-independent PKC Apl II, exist in the Aplysia nervous system. For the first time, we have now been able to functionally determine which isoform of PKC is involved in a particular form of plasticity. We microinjected cultured sensorimotor pairs of neurons with various PKC constructs tagged with the enhanced green fluorescent protein as a reporter for successful plasmid expression. Our results demonstrate that short-term facilitation of depressed synapses is mediated by PKC Apl II. Dominant-negative PKC Apl II, but not dominant-negative PKC Apl I, disrupted the normal kinetics of 5-HT-induced facilitation by completely blocking its rapid onset. This effect was specific to depressed synapses, because dominant-negative PKC Apl II did not inhibit 5-HT-mediated facilitation of nondepressed synapses. Our results suggest that not only different signal transduction pathways but also different isoforms of a specific cascade may mediate physiological responses according to the state of a synapse.

Key words: Aplysia; protein kinase C; memory; synaptic facilitation; serotonin; plasmids

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Copyright © 2001 Society for Neuroscience  0270-6474/01/2141247-10$05.00/0

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