Signals underlying the induction and expression of long-term, injury-related plasticity in sensory neurons of Aplysia

An important goal in the study of long-term memory is to understand the signals that induce and maintain the underlying neural alterations. In Aplysia, long-term sensitization of defensive reflexes has been examined in depth as a simple model of memory. Extensive studies of sensory neurons (SNs) in Aplysia have led to a cellular and molecular model of long-term memory that has greatly influenced memory research. According to this model, induction of long-term memory in Aplysia depends upon serotonin (5-HT) release and subsequent activation of the cAMP-PKA pathway in SNs. The evidence supporting this model mainly came from studies of long-term synaptic facilitation (LTF) using dissociated (and therefore axotomized) cells growing in culture. However, studies in more intact preparations have produced complex and discrepant results. Because these SNs function as nociceptors, and display similar alterations (long-term hyperexcitability [LTH], LTF, and growth) in models of memory and nerve injury, this study examined the roles of 5-HT and the cAMP-PKA pathway in the induction and expression of long-term, injury-related LTH and LTF in Aplysia SNs. The results presented here suggest that 5-HT is not a primary signal for inducing LTH (and perhaps LTF) in Aplysia SNs. Prolonged treatment with 5-HT failed to induce LTH of Aplysia SNs in either ganglia or dissociated-cell preparations. Treatment with a 5-HT antagonist, methiothepin, during noxious nerve stimulation failed to reduce 24 hr LTH. Furthermore, while 5-HT can induce LTF of SN synapses, this LTF appears to be an indirect effect of 5-HT on other cells. When neural activity was suppressed by elevating divalent cations or by using tetrodotoxin (TTX), 5-HT failed to induce LTF. Unlike LTF, LTH of the SNs could not be produced, even when 5-HT treatment occurred in normal artificial sea water (ASW), suggesting that LTH and LTF are likely to depend on different signals for induction. However, methiothepin reduced the later expression of LTH induced by nerve stimulation, suggesting that 5-HT contributes to the maintenance of LTH in Aplysia SNs.n of somata from the ganglion (which axotomizes SNs) or crushing peripheral n. In summary, this study found that 5-HT and the cAMP-PKA pathway are not involved in the induction of long-term, injury-related LTH of Aplysia SNs, but persistent release of 5-HT and persistent PKA activity contribute to the maintenance of LTH induced by injury. (Abstract shortened by UMI.