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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Aplysia
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Arginine / genetics
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Cell Adhesion Molecules, Neuronal / genetics
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Cell Adhesion Molecules, Neuronal / metabolism*
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Cells, Cultured
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Central Nervous System / cytology
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Cloning, Molecular / methods
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Cysteine / genetics
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Green Fluorescent Proteins / genetics
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Humans
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Microinjections / methods
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Molecular Sequence Data
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Motor Neurons / drug effects
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Motor Neurons / physiology*
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Protein Binding / physiology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Sensory Receptor Cells / drug effects
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Sensory Receptor Cells / physiology*
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Serotonin / pharmacology
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Synapses / metabolism
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Synapses / physiology
Substances
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Cell Adhesion Molecules, Neuronal
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Membrane Proteins
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Nerve Tissue Proteins
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Nrxn1 protein, rat
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Oligodeoxyribonucleotides, Antisense
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Receptors, Cell Surface
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neuroligin 3
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Green Fluorescent Proteins
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Serotonin
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Arginine
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Cysteine
Associated data
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GENBANK/HM448446
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GENBANK/HM461999