title: Deficit in long-term synaptic plasticity is rescued by a computationally predicted stimulus protocol.
abstract: Mutations in the gene encoding CREB-binding protein (CBP) cause deficits in long-term plasticity, learning, and memory. Here, long-term synaptic facilitation (LTF) at Aplysia sensorimotor synapses in cell culture was used as a model system to investigate methods for overcoming deficits in LTF produced by a CBP knockdown. Injecting CBP-siRNA into individual sensory neurons reduced CBP levels and impaired LTF produced by a standard protocol of five 5-min pulses of serotonin (5-HT) delivered at 20 min interstimulus intervals. A computational model, which simulated molecular processes underlying LTF induction, predicted a rescue protocol of five pulses of 5-HT at non-uniform interstimulus intervals that overcame the consequences of reduced CBP and restored LTF. These results suggest that complementary empirical and computational studies can identify methods for ameliorating impairments of learning attributable to molecular lesions.
authors.affiliation: Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: Rong-Yu
authors.initials: RY
authors.lastname: Liu
authors.forename: Yili
authors.initials: Y
authors.lastname: Zhang
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.forename: Paul
authors.initials: P
authors.lastname: Smolen
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Cleary
authors.forename: John H
authors.initials: JH
authors.lastname: Byrne
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001048:Aplysia; D001703:Biophysics; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003198:Computer Simulation; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008959:Models, Neurological; D009046:Motor Neurons / Q000166:cytology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011237:Predictive Value of Tests; D034741:RNA, Small Interfering / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000166:cytology; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D012701:Serotonin; D050882:CREB-Binding Protein