Cargando…

Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits

In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as...

Descripción completa

Detalles Bibliográficos
Autores principales: Prince, Luke Y., Bacon, Travis, Humphries, Rachel, Tsaneva-Atanasova, Krasimira, Clopath, Claudia, Mellor, Jack R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513881/
https://www.ncbi.nlm.nih.gov/pubmed/34597293
http://dx.doi.org/10.1371/journal.pcbi.1009435
_version_ 1784583287011803136
author Prince, Luke Y.
Bacon, Travis
Humphries, Rachel
Tsaneva-Atanasova, Krasimira
Clopath, Claudia
Mellor, Jack R.
author_facet Prince, Luke Y.
Bacon, Travis
Humphries, Rachel
Tsaneva-Atanasova, Krasimira
Clopath, Claudia
Mellor, Jack R.
author_sort Prince, Luke Y.
collection PubMed
description In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.
format Online
Article
Text
id pubmed-8513881
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-85138812021-10-14 Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits Prince, Luke Y. Bacon, Travis Humphries, Rachel Tsaneva-Atanasova, Krasimira Clopath, Claudia Mellor, Jack R. PLoS Comput Biol Research Article In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage. Public Library of Science 2021-10-01 /pmc/articles/PMC8513881/ /pubmed/34597293 http://dx.doi.org/10.1371/journal.pcbi.1009435 Text en © 2021 Prince et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Prince, Luke Y.
Bacon, Travis
Humphries, Rachel
Tsaneva-Atanasova, Krasimira
Clopath, Claudia
Mellor, Jack R.
Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
title Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
title_full Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
title_fullStr Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
title_full_unstemmed Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
title_short Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits
title_sort separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal ca3 circuits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513881/
https://www.ncbi.nlm.nih.gov/pubmed/34597293
http://dx.doi.org/10.1371/journal.pcbi.1009435
work_keys_str_mv AT princelukey separableactionsofacetylcholineandnoradrenalineonneuronalensembleformationinhippocampalca3circuits
AT bacontravis separableactionsofacetylcholineandnoradrenalineonneuronalensembleformationinhippocampalca3circuits
AT humphriesrachel separableactionsofacetylcholineandnoradrenalineonneuronalensembleformationinhippocampalca3circuits
AT tsanevaatanasovakrasimira separableactionsofacetylcholineandnoradrenalineonneuronalensembleformationinhippocampalca3circuits
AT clopathclaudia separableactionsofacetylcholineandnoradrenalineonneuronalensembleformationinhippocampalca3circuits
AT mellorjackr separableactionsofacetylcholineandnoradrenalineonneuronalensembleformationinhippocampalca3circuits