Long-Term Effects of Axotomy on Excitability and Growth of Isolated Aplysia Sensory Neurons in Cell Culture: Role of cAMP. Supinder S. Bedi, Ali Salim, Shanping Chen, and David L. Glanzman. Department of Physiological Science, UCLA, 2859 Slichter Hall, Box 951568, Los Angeles, CA 90095-1568. Brain Research Institute, UCLA, Los Angeles, CA 90095.
APStracts 4:320N, 1997.
ABSTRACT
Crushing nerves in Aplysia which contain the axons of central sensory neurons causes the neurons to become hyperexcitable and to sprout new processes. Previous experiments which examined the effects of axonal injury on Aplysia sensory neurons have been performed in the intact animal or in the semi-intact central nervous system of Aplysia. It has therefore been unclear to what extent the long-term neuronal consequences of injury are due to intrinsic or extrinsic cellular signals. To determine whether injury-induced changes in Aplysia sensory neurons are due to intrinsic or extrinsic signals, we have developed an in vitro model of axonal injury. Isolated central sensory neurons grown for 2 days in cell culture were axotomized. Approximately 24 hr after axotomy sensory neurons exhibited a greater excitabilityÄreflected, in part, as a significant reduction in spike accommodationÄand greater neuritic outgrowth than did control (unaxotomized) neurons. Rp-cAMPS, an inhibitor of protein kinase A, blocked both the reduction in accommodation and increased neuritic outgrowth induced by axotomy. Rp- cAMPS also blocked similar, albeit smaller, alterations observed in control sensory neurons over the 24-hr period of our experiments. These results indicate that axonal injury elevates cAMP levels within Aplysia sensory neurons, and that this elevation is directly responsible, in part, for the previously described long-term electrophysiological and morphological changes induced in Aplysia sensory neurons by nerve crush. In addition, the results indicate that control sensory neurons in culture are also undergoing injury-related electrophysiological and structural changes, probably due to cellular processes triggered when the neurons are axotomized during cell culturing. Finally, the results provide support for the idea that the cellular processes activated within Aplysia sensory neurons by injury, and those activated during long-term behavioral sensitization, overlap significantly.

Received 19 November 1996; accepted in final form 11 November 1997.
APS Manuscript Number J918-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997