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Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum

Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs, although their exact function has remained controversial. Her...

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Autores principales: Chipman, Peter H, Fung, Chi Chung Alan, Pazo Fernandez, Alejandra, Sawant, Abhilash, Tedoldi, Angelo, Kawai, Atsushi, Ghimire Gautam, Sunita, Kurosawa, Mizuki, Abe, Manabu, Sakimura, Kenji, Fukai, Tomoki, Goda, Yukiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594917/
https://www.ncbi.nlm.nih.gov/pubmed/34693906
http://dx.doi.org/10.7554/eLife.70818
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author Chipman, Peter H
Fung, Chi Chung Alan
Pazo Fernandez, Alejandra
Sawant, Abhilash
Tedoldi, Angelo
Kawai, Atsushi
Ghimire Gautam, Sunita
Kurosawa, Mizuki
Abe, Manabu
Sakimura, Kenji
Fukai, Tomoki
Goda, Yukiko
author_facet Chipman, Peter H
Fung, Chi Chung Alan
Pazo Fernandez, Alejandra
Sawant, Abhilash
Tedoldi, Angelo
Kawai, Atsushi
Ghimire Gautam, Sunita
Kurosawa, Mizuki
Abe, Manabu
Sakimura, Kenji
Fukai, Tomoki
Goda, Yukiko
author_sort Chipman, Peter H
collection PubMed
description Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs, although their exact function has remained controversial. Here, we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron.
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spelling pubmed-85949172021-11-17 Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum Chipman, Peter H Fung, Chi Chung Alan Pazo Fernandez, Alejandra Sawant, Abhilash Tedoldi, Angelo Kawai, Atsushi Ghimire Gautam, Sunita Kurosawa, Mizuki Abe, Manabu Sakimura, Kenji Fukai, Tomoki Goda, Yukiko eLife Neuroscience Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs, although their exact function has remained controversial. Here, we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron. eLife Sciences Publications, Ltd 2021-10-25 /pmc/articles/PMC8594917/ /pubmed/34693906 http://dx.doi.org/10.7554/eLife.70818 Text en © 2021, Chipman et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Chipman, Peter H
Fung, Chi Chung Alan
Pazo Fernandez, Alejandra
Sawant, Abhilash
Tedoldi, Angelo
Kawai, Atsushi
Ghimire Gautam, Sunita
Kurosawa, Mizuki
Abe, Manabu
Sakimura, Kenji
Fukai, Tomoki
Goda, Yukiko
Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
title Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
title_full Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
title_fullStr Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
title_full_unstemmed Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
title_short Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum
title_sort astrocyte glun2c nmda receptors control basal synaptic strengths of hippocampal ca1 pyramidal neurons in the stratum radiatum
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594917/
https://www.ncbi.nlm.nih.gov/pubmed/34693906
http://dx.doi.org/10.7554/eLife.70818
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