title: Persistent long-term synaptic plasticity requires activation of a new signaling pathway by additional stimuli.
abstract: Most memories are strengthened by additional stimuli, but it is unclear how additional stimulation or training reinforces long-term memory. To address this we examined whether long-term facilitation (LTF) of Aplysia sensorimotor synapses in cell culture-a cellular correlate of long-term sensitization of defensive withdrawal reflexes in Aplysia californica-can be prolonged by additional stimulation. We found that 1 d treatment with serotonin (5-HT; five brief applications at 20 min intervals) produced LTF lasting ∼3 d, whereas 2 d of such 5-HT treatments induced a persistent LTF lasting >7 d. Incubation with the protein synthesis inhibitor rapamycin during the second set of 5-HT treatments abolished all facilitation, and synapse strength returned prematurely to baseline. Persistent LTF required more persistent elevation in the expression of the neurotrophin-like peptide sensorin and its secretion. Activation of protein kinase C (PKC) during the second day of 5-HT treatments, not required for LTF or changes in sensorin expression during the first set of 5-HT treatments, is critical for persistent LTF and replaces phosphoinositide 3 kinase (PI3K) activity in mediating the increase in sensorin expression. In contrast, activations of PKC during the first day of 5-HT treatments and PI3K during the second day of 5-HT treatments are unnecessary for persistent LTF or the increases in sensorin expression. Thus, additional stimuli make preexisting plasticity labile as they recruit a new signaling cascade to regulate the synthesis of a neurotrophin-like peptide required for persistent alterations in synaptic efficacy.
authors.affiliation: Department of Neuroscience, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York 10032, USA. jh2004@columbia.edu
authors.forename: Jiang-Yuan
authors.initials: JY
authors.lastname: Hu
authors.forename: Orit
authors.initials: O
authors.lastname: Baussi
authors.forename: Amir
authors.initials: A
authors.lastname: Levine
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Samuel
authors.initials: S
authors.lastname: Schacher
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001048:Aplysia; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017952:Ganglia, Invertebrate / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000276:immunology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009479:Neuropeptides; C419310:sensorin A protein, Aplysia; D012701:Serotonin; D011493:Protein Kinase C; D020123:Sirolimus