Memory-like alterations in Aplysia axons after nerve injury or localized depolarization.

Adaptive, long-term alterations of excitability have been reported in dendrites and presynaptic terminals but not along axons. Persistent enhancement of axonal excitability has been described in proximal nerve stumps at sites of nerve section in mammals, but this hyperexcitability is considered a pathological derangement important only as a cause of neuropathic pain. Identified neurons in Aplysia were used to test the hypothesis that either axonal injury or the focal depolarization that accompanies axonal injury can trigger a local decrease in action potential threshold [long-term hyperexcitability (LTH)] having memory-like properties. Nociceptive tail sensory neurons and a giant secretomotor neuron, R2, exhibited localized axonal LTH lasting 24 hr after a crush of the nerve or connective that severed the tested axons. Axons of tail sensory neurons and tail motor neurons, but not R2, displayed similar localized LTH after peripheral depolarization produced by 2 min exposure to elevated extracellular [K(+)]. Neither the induction nor expression of either form of LTH was blocked by saline containing 1% normal [Ca(2+)] during treatment or testing. However, both were prevented by local application of the protein synthesis inhibitors anisomycin or rapamycin. The features of (1) long-lasting alteration by localized depolarization, (2) restriction of alterations to intensely depolarized regions, and (3) dependence of the alterations on local, rapamycin-sensitive protein synthesis are shared with synaptic mechanisms considered important for memory formation. This commonality suggests that relatively simple, accessible axons may offer an opportunity to define fundamental plasticity mechanisms that were important in the evolution of memory.