Axoplasm enriched in a protein mobilized by nerve injury induces memory-like alterations in Aplysia neurons.
Axon regeneration after injury and long-term alterations associated with learning both require protein synthesis in the neuronal cell body, but the signals that initiate these changes are largely unknown. Direct evidence that axonal injury activates molecular signals in the axon was obtained by injecting axoplasm from crushed or uncrushed nerves into somata of sensory neurons with uncrushed axons. Those injected with crush axoplasm behaved as if their axons had been crushed, exhibiting increases in both repetitive firing and spike duration, and a decrease in spike afterhyperpolarization 1 d after injection. Because similar changes occur in the same cells after learning, these data suggest that some of the long-lasting adaptive changes that occur after injury and learning may be induced by common axoplasmic signals. Since the signals in axoplasm must be conveyed to the cell soma, we have begun to test the hypothesis that at least some of these signals are proteins containing a nuclear localization signal (NLS). Axoplasmic proteins at the crush site and those that accumulated at a ligation proximal to the crush were probed with an antibody to an amino acid sequence (sp) containing a NLS that provides access to the retrograde transport/nuclear import pathway. One protein, sp97, displayed properties expected of an axonal injury signal: it responded to injury by undergoing an anterograde-to-retrograde change in movement and, when the ligation was omitted, it was transported to the cell bodies of the injured neurons.
Ambron
R T
RT
Department of Anatomy, Columbia University, New York, New York 10032, USA.
Dulin
M F
MF
Zhang
X P
XP
Schmied
R
R
Walters
E T
ET
D000818:Animals; D001048:Aplysia; D001370:Axonal Transport; D001369:Axons / Q000502:physiology*; D005071:Evoked Potentials; D008568:Memory / Q000502:physiology*; D009409:Nerve Crush; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D013997:Time Factors
D009419:Nerve Tissue Proteins