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

Jon Palacios-Filardo, Matt Udakis, Giles A. Brown, Benjamin G. Tehan, Miles S. Congreve, Pradeep J. Nathan, Alastair J. H. Brown and Jack R. Mellor ()
Additional contact information
Jon Palacios-Filardo: University of Bristol, University Walk
Matt Udakis: University of Bristol, University Walk
Giles A. Brown: Sosei Heptares, Steinmetz Building, Granta Park, Great Abingdon
Benjamin G. Tehan: Sosei Heptares, Steinmetz Building, Granta Park, Great Abingdon
Miles S. Congreve: Sosei Heptares, Steinmetz Building, Granta Park, Great Abingdon
Pradeep J. Nathan: University of Cambridge
Alastair J. H. Brown: Sosei Heptares, Steinmetz Building, Granta Park, Great Abingdon
Jack R. Mellor: University of Bristol, University Walk

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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 M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25280-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25280-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25280-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().