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Cholinergic modulation of Up–Down states in the mouse medial entorhinal cortex in vitro

Hay, YA; Jarzebowski, P; Zhang, Y; Digby, R; Brendel, V; Paulsen, O; Magloire, V; (2021) Cholinergic modulation of Up–Down states in the mouse medial entorhinal cortex in vitro. European Journal of Neuroscience , 53 (5) pp. 1378-1393. 10.1111/ejn.15032. Green open access

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Abstract

Cholinergic tone is high during wake and rapid eye movement sleep and lower during slow wave sleep (SWS). Nevertheless, the low tone of acetylcholine during SWS modulates sharp wave ripple incidence in the hippocampus and slow wave activity in the neocortex. Linking the hippocampus and neocortex, the medial entorhinal cortex (mEC) regulates the coupling between these structures during SWS, alternating between silent Down states and active Up states, which outlast neocortical ones. Here, we investigated how low physiological concentrations of acetylcholine (ACh; 100‐500 nM) modulate Up and Down states in a mEC slice preparation. We find that ACh has a dual effect on mEC activity: it prolongs apparent Up state duration as recorded in individual cells and decreases the total synaptic charge transfer, without affecting the duration of detectable synaptic activity. The overall outcome of ACh application is excitatory and we show that ACh increases Up state incidence via muscarinic receptor activation. The mean firing rate of principal neurons increased in around half of the cells while the other half showed a decrease in firing rate. Using two‐photon calcium imaging of population activity, we found that population‐wide network events are more frequent and rhythmic during ACh and confirmed that ACh modulates cell participation in these network events, consistent with a role for cholinergic modulation in regulating information flow between the hippocampus and neocortex during SWS.

Type: Article
Title: Cholinergic modulation of Up–Down states in the mouse medial entorhinal cortex in vitro
Location: France
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ejn.15032
Publisher version: https://doi.org/10.1111/ejn.15032
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Acetylcholine, Network synchrony, Population calcium imaging, Slow wave sleep, Spontaneous activity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Experimental Psychology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/10115751
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