title: Neurexin-neuroligin transsynaptic interaction mediates learning-related synaptic remodeling and long-term facilitation in aplysia.
abstract: Neurexin and neuroligin, which undergo heterophilic interactions with each other at the synapse, are mutated in some patients with autism spectrum disorder, a set of disorders characterized by deficits in social and emotional learning. We have explored the role of neurexin and neuroligin at sensory-to-motor neuron synapses of the gill-withdrawal reflex in Aplysia, which undergoes sensitization, a simple form of learned fear. We find that depleting neurexin in the presynaptic sensory neuron or neuroligin in the postsynaptic motor neuron abolishes both long-term facilitation and the associated presynaptic growth induced by repeated pulses of serotonin. Moreover, introduction into the motor neuron of the R451C mutation of neuroligin-3 linked to autism spectrum disorder blocks both intermediate-term and long-term facilitation. Our results suggest that activity-dependent regulation of the neurexin-neuroligin interaction may govern transsynaptic signaling required for the storage of long-term memory, including emotional memory that may be impaired in autism spectrum disorder.
authors.affiliation: Department of Neurology, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Choi
authors.forename: Hsiu-Ling
authors.initials: HL
authors.lastname: Li
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Kassabov
authors.forename: Iksung
authors.initials: I
authors.lastname: Jin
authors.forename: Sathyanarayanan V
authors.initials: SV
authors.lastname: Puthanveettil
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Karl
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bailey
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001048:Aplysia; D001120:Arginine / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D003001:Cloning, Molecular / Q000379:methods; D003545:Cysteine / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008845:Microinjections / Q000379:methods; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C547193:Nrxn1 protein, rat; D020319:Oligodeoxyribonucleotides, Antisense; D011956:Receptors, Cell Surface; C098004:neuroligin 3; D049452:Green Fluorescent Proteins; D012701:Serotonin; D001120:Arginine; D003545:Cysteine