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Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus
The receptor deleted in colorectal cancer (DCC) and its ligand netrin-1 are essential for axon guidance during development and are expressed by neurons in the mature brain. Netrin-1 recruits GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and is critical for...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137442/ https://www.ncbi.nlm.nih.gov/pubmed/32264905 http://dx.doi.org/10.1186/s13041-020-00597-2 |
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author | Glasgow, Stephen D. Wong, Edwin W. Thompson-Steckel, Greta Marcal, Nathalie Séguéla, Philippe Ruthazer, Edward S. Kennedy, Timothy E. |
author_facet | Glasgow, Stephen D. Wong, Edwin W. Thompson-Steckel, Greta Marcal, Nathalie Séguéla, Philippe Ruthazer, Edward S. Kennedy, Timothy E. |
author_sort | Glasgow, Stephen D. |
collection | PubMed |
description | The receptor deleted in colorectal cancer (DCC) and its ligand netrin-1 are essential for axon guidance during development and are expressed by neurons in the mature brain. Netrin-1 recruits GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and is critical for long-term potentiation (LTP) at CA3-CA1 hippocampal Schaffer collateral synapses, while conditional DCC deletion from glutamatergic neurons impairs hippocampal-dependent spatial memory and severely disrupts LTP induction. DCC co-fractionates with the detergent-resistant component of postsynaptic density, yet is enriched in axonal growth cones that differentiate into presynaptic terminals during development. Specific presynaptic and postsynaptic contributions of DCC to the function of mature neural circuits have yet to be identified. Employing hippocampal subregion-specific conditional deletion of DCC, we show that DCC loss from CA1 hippocampal pyramidal neurons resulted in deficits in spatial memory, increased resting membrane potential, abnormal dendritic spine morphology, weaker spontaneous excitatory postsynaptic activity, and reduced levels of postsynaptic adaptor and signaling proteins; however, the capacity to induce LTP remained intact. In contrast, deletion of DCC from CA3 neurons did not induce detectable changes in the intrinsic electrophysiological properties of CA1 pyramidal neurons, but impaired performance on the novel object place recognition task as well as compromised excitatory synaptic transmission and LTP at Schaffer collateral synapses. Together, these findings reveal specific pre- and post-synaptic contributions of DCC to hippocampal synaptic plasticity underlying spatial memory. |
format | Online Article Text |
id | pubmed-7137442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71374422020-04-11 Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus Glasgow, Stephen D. Wong, Edwin W. Thompson-Steckel, Greta Marcal, Nathalie Séguéla, Philippe Ruthazer, Edward S. Kennedy, Timothy E. Mol Brain Research The receptor deleted in colorectal cancer (DCC) and its ligand netrin-1 are essential for axon guidance during development and are expressed by neurons in the mature brain. Netrin-1 recruits GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and is critical for long-term potentiation (LTP) at CA3-CA1 hippocampal Schaffer collateral synapses, while conditional DCC deletion from glutamatergic neurons impairs hippocampal-dependent spatial memory and severely disrupts LTP induction. DCC co-fractionates with the detergent-resistant component of postsynaptic density, yet is enriched in axonal growth cones that differentiate into presynaptic terminals during development. Specific presynaptic and postsynaptic contributions of DCC to the function of mature neural circuits have yet to be identified. Employing hippocampal subregion-specific conditional deletion of DCC, we show that DCC loss from CA1 hippocampal pyramidal neurons resulted in deficits in spatial memory, increased resting membrane potential, abnormal dendritic spine morphology, weaker spontaneous excitatory postsynaptic activity, and reduced levels of postsynaptic adaptor and signaling proteins; however, the capacity to induce LTP remained intact. In contrast, deletion of DCC from CA3 neurons did not induce detectable changes in the intrinsic electrophysiological properties of CA1 pyramidal neurons, but impaired performance on the novel object place recognition task as well as compromised excitatory synaptic transmission and LTP at Schaffer collateral synapses. Together, these findings reveal specific pre- and post-synaptic contributions of DCC to hippocampal synaptic plasticity underlying spatial memory. BioMed Central 2020-04-07 /pmc/articles/PMC7137442/ /pubmed/32264905 http://dx.doi.org/10.1186/s13041-020-00597-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Glasgow, Stephen D. Wong, Edwin W. Thompson-Steckel, Greta Marcal, Nathalie Séguéla, Philippe Ruthazer, Edward S. Kennedy, Timothy E. Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus |
title | Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus |
title_full | Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus |
title_fullStr | Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus |
title_full_unstemmed | Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus |
title_short | Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus |
title_sort | pre- and post-synaptic roles for dcc in memory consolidation in the adult mouse hippocampus |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137442/ https://www.ncbi.nlm.nih.gov/pubmed/32264905 http://dx.doi.org/10.1186/s13041-020-00597-2 |
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