Cited by 147Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenetics and Neurodevelopmental Disorders

DCC expression by neurons regulates synaptic plasticity in the adult brain

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Horn, Katherine E., Glasgow, Stephen D., Gobert, Delphine, Bull, Sarah-Jane, Luk, Tamarah, Girgis, Jacklyn, Tremblay, Marie-Eve, McEachern, Danielle +10 more·2013·Cell Reports

Abstract

The transmembrane protein deleted in colorectal cancer (DCC) and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP), intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR) function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

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Crossref · 10.1016/j.celrep.2012.12.005

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  • Plcg2 in granule cells may be relevant for synaptic transmission and plasticity via induction of hippocampal long-term potentiation (LTP).

    “By analogy with Plcg1 function in neurons, Plcg2 in granule cells may be relevant for synaptic transmission and plasticity via induction of hippocampal long-term potentiation LTP [10, 44].”

    From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [44]

    The section “DCC Regulates Src, Phospholipase C γ, and Phosphorylated Src Family Kinase Expression” (p. 7) reports reduced PLCγ1 activation in DCC-deficient hippocampi, and “Src Is Essential for LTP Induction” (p. 10) links PLC signaling to LTP. These passages support the Plcg1 analogy, but the paper does not establish a role for Plcg2 in granule cells or show that it induces LTP. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • DCC shows abundant expression in dopaminergic neurons, and DCC-deficient mice show altered dopaminergic system organization, culminating in impaired memory, behavior, and reward responses.

    “This gene shows abundant expression in dopaminergic neurons, and behavioral studies of DCC-deficient mice show altered dopaminergic system organization, culminating in impaired memory, behavior, and reward responses (46,47).”

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Authors
Horn, K. E., Glasgow, S. D., Gobert, D., Bull, S.-J., Luk, T., Girgis, J., Tremblay, M.-E., McEachern, D., Bouchard, J.-F., Haber, M., Hamel, E., Krimpenfort, P., Murai, K. K., Berns, A., Doucet, G., Chapman, C. A., Ruthazer, E. S., & Kennedy, T. E.
Affiliations
  • Montreal Neurological Institute and Hospital (CA)
  • Concordia University (CA)
  • Montreal General Hospital (CA)
  • The Netherlands Cancer Institute (NL)
  • Université de Montréal (CA)
Venue
Cell Reports
Publisher
Elsevier BV
Published
2013-01
Volume
3
Issue
1
Pages
173-185
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2129722759
Cited by
147
References
59
Citations by year
2026: 9 · 2025: 9 · 2024: 16 · 2023: 11 · 2022: 12 · 2021: 6 · 2020: 20 · 2019: 13 · 2018: 12 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 10
FWCI
4.74
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship@McGill (McGill) (submittedVersion)
Funders
  • Killam Trusts
  • Canadian Institutes of Health Research (247564)
  • Natural Sciences and Engineering Research Council of Canada
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
DCC, netrin-1, synaptic plasticity, long-term potentiation, long-term depression, dendritic spines, Src kinase, NMDA receptor, memory formation, neuronal adhesion, forebrain, pyramidal neurons, learning and memory
MeSH terms
Netrin-1, DCC Receptor, Aging, Animals, Brain, Enzyme Activation, Hippocampus, Memory, Nerve Growth Factors, Neuronal Plasticity, Neurons, Phosphorylation, Receptors, Cell Surface, Subcellular Fractions, Synapses, Receptors, N-Methyl-D-Aspartate, Prosencephalon, Gene Deletion, Long-Term Potentiation, Maze Learning, src-Family Kinases, Tumor Suppressor Proteins, Dendritic Spines, Mice, Rats, Phospholipase C gamma

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