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The Journal of Neuroscience, December 15, 2001, 21(24):9667-9677

Axonal Rejoining Inhibits Injury-Induced Long-Term Changes in Aplysia Sensory Neurons In Vitro

Supinder S. Bedi1 and David L. Glanzman1, 2

1 Department of Neurobiology, School of Medicine, University of California, Los Angeles, California 90095-1763, and 2 Department of Physiological Science and the Brain Research Institute, University of California, Los Angeles, California 90095-1761

Injury of Aplysia sensory neurons, both in the CNS and in dissociated cell culture, produces long-term changes in these cells, among which are hyperexcitability and enhanced neuritic outgrowth (hypermorphogenesis). These long-term, injury-induced changes are attributable, in part, to the generation of new intrinsic cellular signals. Little is known, however, about the signals that maintain homeostasis within sensory neurons. To elucidate the role of homeostatic signals in Aplysia sensory neurons, we investigated how axonal rejoining alters the cellular consequences of axotomy. Sensory neurons in dissociated cell culture were axotomized. In some cases, the distal segment of the severed axon was then removed; in other cases, the proximal and distal segments of the severed axon were permitted to rejoin. If the severed distal segment was left unmolested, then axonal rejoining invariably occurred within 7 hr. Surprisingly, we found that the characteristic long-term cellular consequences of axotomy were suppressed by axonal rejoining. The long-term axotomy-induced changes were not inhibited merely by contact between the severed axon and another, uninjured sensory neuron. These results indicate that long-term changes in sensory neurons induced by injury are attributable, in part, to prolonged disruption of a retrograde homeostatic signal that originates in the distal segment of the growing neurite and chronically suppresses hyperexcitability and hypermorphogenesis.

Key words: regeneration; homeostatic signals; neural plasticity; neural repair; axotomy; hyperexcitability; neuritogenesis


Copyright © 2001 Society for Neuroscience  0270-6474/01/21249667-11$05.00/0


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