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