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Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressi...

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Autores principales: Palacios-Filardo, Jon, Udakis, Matt, Brown, Giles A., Tehan, Benjamin G., Congreve, Miles S., Nathan, Pradeep J., Brown, Alastair J. H., Mellor, Jack R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445995/
https://www.ncbi.nlm.nih.gov/pubmed/34531380
http://dx.doi.org/10.1038/s41467-021-25280-5
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author Palacios-Filardo, Jon
Udakis, Matt
Brown, Giles A.
Tehan, Benjamin G.
Congreve, Miles S.
Nathan, Pradeep J.
Brown, Alastair J. H.
Mellor, Jack R.
author_facet Palacios-Filardo, Jon
Udakis, Matt
Brown, Giles A.
Tehan, Benjamin G.
Congreve, Miles S.
Nathan, Pradeep J.
Brown, Alastair J. H.
Mellor, Jack R.
author_sort Palacios-Filardo, Jon
collection PubMed
description Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M(3) and M(4) receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.
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spelling pubmed-84459952021-10-04 Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits Palacios-Filardo, Jon Udakis, Matt Brown, Giles A. Tehan, Benjamin G. Congreve, Miles S. Nathan, Pradeep J. Brown, Alastair J. H. Mellor, Jack R. Nat Commun Article Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M(3) and M(4) receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation. Nature Publishing Group UK 2021-09-16 /pmc/articles/PMC8445995/ /pubmed/34531380 http://dx.doi.org/10.1038/s41467-021-25280-5 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Palacios-Filardo, Jon
Udakis, Matt
Brown, Giles A.
Tehan, Benjamin G.
Congreve, Miles S.
Nathan, Pradeep J.
Brown, Alastair J. H.
Mellor, Jack R.
Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
title Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
title_full Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
title_fullStr Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
title_full_unstemmed Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
title_short Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
title_sort acetylcholine prioritises direct synaptic inputs from entorhinal cortex to ca1 by differential modulation of feedforward inhibitory circuits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445995/
https://www.ncbi.nlm.nih.gov/pubmed/34531380
http://dx.doi.org/10.1038/s41467-021-25280-5
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