Intrinsic Injury Signals Enhance Growth, Survival, and Excitability of<i>Aplysia</i>Neurons

Abstract

Neurons undergo extensive changes in growth and electrophysiological properties in response to axon injury. Efforts to understand the molecular mechanisms that initiate these changes have focused almost exclusively on the role of extrinsic signals, primarily neurotrophic factors released from target and glial cells. The objective of the present investigation was to determine whether the response to axonal injury also involves intrinsic axoplasmic signals. Aplysia neurons were removed from their ganglia and placed in vitro on a substratum permissive for growth, but in the absence of glia and soluble growth factors. Under these conditions, neurites emerged and grew for approximately 4 d. Once growth had ceased, the neurites were transected. In all, 46 of 50 cells regenerated, either by resorbing the remaining neurites and elaborating a new neuritic arbor or by merely replacing the neurites that had been severed. Cut cells also exhibited enhanced excitability and, paradoxically, prolonged survival, when compared with uninjured neurons. These findings indicate that axons contain intrinsic molecular signals that are directly activated by injury to trigger changes underlying regeneration and compensatory plasticity.