Neurexin-Neuroligin Transsynaptic Interaction Mediates Learning-Related Synaptic Remodeling and Long-Term Facilitation in Aplysia
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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.
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Neuroligins regulate the activity-dependent maturation and modulation of synapses.
“Notably, neuroligins have been found to regulate the activity-dependent maturation and modulation of synapses.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [43]
Overexpression of neuroligin with an ASD-associated mutation blocked intermediate and long-term facilitation at the sensory-to-motor neuron synapse, relative to wild-type neuroligin.
“Relative to wild-type neuroligin, overexpression of neuroligin with an ASD-associated mutation blocked intermediate and long-term facilitation at the sensory-to-motor neuron synapse43.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [43]
Reference 43 shows in Aplysia that the neurexin-neuroligin interaction controls activity-dependent synaptic development and plasticity, and that an ASD-associated neuroligin mutation disrupts this process.
“Using the Aplysia model system, this study demonstrates that the neurexin-neuroligin interaction regulates activity-dependent synaptic development and plasticity, a process that is dysregulated by an ASD-associated mutation in neuroligin.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [43]
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- Authors
- Choi, Y.-B., Li, H.-L., Kassabov, S. R., Jin, I., Puthanveettil, S. V., Karl, K. A., Lu, Y., Kim, J.-H., Bailey, C. H., & Kandel, E. R.
- Affiliations
- New York State Psychiatric Institute (US)
- Howard Hughes Medical Institute (US)
- Pohang University of Science and Technology (KR)
- Corresponding author
- Kandel, Eric R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 70
- Issue
- 3
- Pages
- 468-481
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3136118
- OpenAlex
- W2152997919
- Cited by
- 94
- References
- 53
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 12 · 2014: 14 · 2013: 12 · 2012: 17
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 808 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Simons Foundation
- National Institutes of Health (NS053415)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- neurexin, neuroligins, trans-synaptic signaling, synaptic remodeling, long-term facilitation, gill-withdrawal reflex, Aplysia, autism spectrum disorder, serotonin, sensitization, emotional memory
- MeSH terms
- Analysis of Variance, Animals, Aplysia, Arginine, Cells, Cultured, Central Nervous System, Cloning, Molecular, Cysteine, Gene Expression Regulation, Humans, Membrane Proteins, Microinjections, Molecular Sequence Data, Motor Neurons, Mutation, Nerve Tissue Proteins, Protein Binding, Receptors, Cell Surface, Sensory Receptor Cells, Serotonin, Synapses, Cell Adhesion Molecules, Neuronal, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Oligodeoxyribonucleotides, Antisense, Green Fluorescent Proteins
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