title: Persistent Associative Plasticity at an Identified Synapse Underlying Classical Conditioning Becomes Labile with Short-Term Homosynaptic Activation.
abstract: Synapses express different forms of plasticity that contribute to different forms of memory, and both memory and plasticity can become labile after reactivation. We previously reported that a persistent form of nonassociative long-term facilitation (PNA-LTF) of the sensorimotor synapses in Aplysia californica, a cellular analog of long-term sensitization, became labile with short-term heterosynaptic reactivation and reversed when the reactivation was followed by incubation with the protein synthesis inhibitor rapamycin. Here we examined the reciprocal impact of different forms of short-term plasticity (reactivations) on a persistent form of associative long-term facilitation (PA-LTF), a cellular analog of classical conditioning, which was expressed at Aplysia sensorimotor synapses when a tetanic stimulation of the sensory neurons was paired with a brief application of serotonin on 2 consecutive days. The expression of short-term homosynaptic plasticity [post-tetanic potentiation or homosynaptic depression (HSD)], or short-term heterosynaptic plasticity [serotonin-induced facilitation or neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa)-induced depression], at synapses expressing PA-LTF did not affect the maintenance of PA-LTF. The kinetics of HSD was attenuated at synapses expressing PA-LTF, which required activation of protein kinase C (PKC). Both PA-LTF and the attenuated kinetics of HSD were reversed by either a transient blockade of PKC activity or a homosynaptic, but not heterosynaptic, reactivation when paired with rapamycin. These results indicate that two different forms of persistent synaptic plasticity, PA-LTF and PNA-LTF, expressed at the same synapse become labile when reactivated by different stimuli.
  
  
  CONCLUSIONS
  Activity-dependent changes in neural circuits mediate long-term memories. Some forms of long-term memories become labile and can be reversed with specific types of reactivations, but the mechanism is complex. At the cellular level, reactivations that induce a reversal of memory must evoke changes in neural circuits underlying the memory. What types of reactivations induce a labile state at neural connections that lead to reversal of different types of memory? We find that a critical neural connection in Aplysia, which is modified with different stimuli that mediate different types of memory, becomes labile with different types of reactivations. These results provide insights for developing strategies in alleviating maladaptive memories accompanying anxiety disorders.
authors.affiliation: Department of Neuroscience, Columbia University Medical Center, New York State Psychiatric Institute, New York, New York 10032 jh2004@cumc.columbia.edu.
authors.forename: Jiangyuan
authors.identifier: http://orcid.org/0000-0002-4893-1862
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neuroscience, Columbia University Medical Center, New York State Psychiatric Institute, New York, New York 10032.
authors.forename: Samuel
authors.identifier: http://orcid.org/0000-0003-2838-2779
authors.initials: S
authors.lastname: Schacher
mesh_terms: D000818:Animals; D001048:Aplysia; D053119:Benzophenanthridines / Q000494:pharmacology; D001703:Biophysics; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D003214:Conditioning, Classical / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019835:FMRFamide / Q000494:pharmacology; D017950:Ganglia, Sensory / Q000166:cytology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011758:Pyrroles / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D053119:Benzophenanthridines; D002227:Carbazoles; D004791:Enzyme Inhibitors; D011758:Pyrroles; D012701:Serotonin; C057416:KT 5720; D019835:FMRFamide; C016299:chelerythrine
keywords: Aplysia; heterosynaptic activity; homosynaptic activity; protein kinase C; protein synthesis; reconsolidation