title: Serotonin induces memory-like, rapamycin-sensitive hyperexcitability in sensory axons of aplysia that contributes to injury responses.
abstract: The induction of long-term facilitation (LTF) of synapses of Aplysia sensory neurons (SNs) by serotonin (5-HT) has provided an important mechanistic model of memory, but little is known about other long-term effects of 5-HT on sensory properties. Here we show that crushing peripheral nerves results in long-term hyperexcitability (LTH) of the axons of these nociceptive SNs that requires 5-HT activity in the injured nerve. Serotonin application to a nerve segment induces local axonal (but not somal) LTH that is inhibited by 5-HT-receptor antagonists. Blockade of crush-induced axonal LTH by an antagonist, methiothepin, provides evidence for mediation of this injury response by 5-HT. This is the first demonstration in any axon of neuromodulator-induced LTH, a phenomenon potentially important for long-lasting pain. Methiothepin does not reduce axonal LTH induced by local depolarization, so 5-HT is not required for all forms of axonal LTH. Serotonin-induced axonal LTH is expressed as reduced spike threshold and increased repetitive firing, whereas depolarization-induced LTH involves only reduced threshold. Like crush- and depolarization-induced LTH, 5-HT-induced LTH is blocked by inhibiting protein synthesis. Blockade by rapamycin, which also blocks synaptic LTF, is interesting because the eukaryotic protein kinase that is the target of rapamycin (TOR) has a conserved role in promoting growth by stimulating translation of proteins required for translation. Rapamycin sensitivity suggests that localized increases in translation of proteins that promote axonal conduction and excitability at sites of nerve injury may be regulated by the same signals that increase translation of proteins that promote neuronal growth.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas-Houston Medical School, 6431 Fannin Blvd. MSB 4.116, Houston, TX 77030, USA.
authors.forename: Ramal M S
authors.initials: RM
authors.lastname: Weragoda
authors.forename: Edgar T
authors.initials: ET
authors.lastname: Walters
mesh_terms: D000818:Animals; D001048:Aplysia / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009409:Nerve Crush; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D012701:Serotonin; D020123:Sirolimus