Memory-Like Alterations inAplysiaAxons after Nerve Injury or Localized Depolarization

Abstract

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 ϩ ]. Neither the induction nor expression of either form of LTH was blocked by saline containing 1% normal [Ca 2ϩ ] 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.

Decreased Nociceptive Sensitization in Mice Lacking the Fragile X Mental Retardation Protein: Role of mGluR1/5 and mTOR

“…Several experiments have demonstrated that dorsal root ganglion axons are translationally competent (Zheng et al, 2001;Willis et al, 2005) and that axonal translation is important for growth cone guidance and collapse (Verma et al, 2005;Wu et al, 2005) and for injury-or depolarization-induced hyperexcitability of Aplysia sensory axons (Weragoda et al, 2004). We have previously demonstrated that FMRP is transported to the peripheral axons of rat nociceptors (Price et al, 2006).…”

“…Axonally synthesized proteins appear to play an important role in nerve regeneration and repair after injury (Willis and Twiss, 2006), and local, axonal translation is required for injuryinduced hyperexcitability of Aplysia axons (Weragoda et al, 2004). We predicted that, if FMRP regulates the translation of proteins that mediate nerve injury-induced hyperexcitability in axons, the development of neuropathic allodynia would be delayed (because these proteins would have to be transported from the soma, rather than synthesized locally) or even absent in Fmr1 KO mice.…”

Axon Physiology

“…Beyond morphological rearrangements, the axon is also able to express many forms of functional plasticity (520,557). In fact, several lines of evidence suggest that ion channel activity is highly regulated by synaptic or neuronal activity (reviews in Refs.…”

Molluscan Memory of Injury: Evolutionary Insights into Chronic Pain and Neurological Disorders

“…These include axonal regeneration and sprouting of neurites near a site of peripheral injury and within central ganglia [Billy and Walters, 1989;Steffensen et al, 1995]. Peripheral injury also causes a decrease in mechanosensory threshold in the damaged region [Billy and Walters, 1989;Dulin et al, 1995], a decrease in electrical threshold of the nociceptor axon near a site of injury or of intense, transient depolarization [Weragoda et al, 2004], and an increase in excitability of the nociceptor soma . Soma hyperexcitability promotes afterdischarge ( fig.…”