Toggle Main Menu Toggle Search

Open Access padlockePrints

Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability

Lookup NU author(s): Dr Rob Graham, Dr Laura AlberioORCiD, Dr Luciano Saieva, Dr Darren Walsh, Professor Andrew Trevelyan


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


© 2023, The Author(s).Cortical activity patterns are strongly modulated by fast synaptic inhibition mediated through ionotropic, chloride-conducting receptors. Consequently, chloride homeostasis is ideally placed to regulate activity. We therefore investigated the stability of baseline [Cl-]i in adult mouse neocortex, using in vivo two-photon imaging. We found a two-fold increase in baseline [Cl-]i in layer 2/3 pyramidal neurons, from day to night, with marked effects upon both physiological cortical processing and seizure susceptibility. Importantly, the night-time activity can be converted to the day-time pattern by local inhibition of NKCC1, while inhibition of KCC2 converts day-time [Cl-]i towards night-time levels. Changes in the surface expression and phosphorylation of the cation-chloride cotransporters, NKCC1 and KCC2, matched these pharmacological effects. When we extended the dark period by 4 h, mice remained active, but [Cl-]i was modulated as for animals in normal light cycles. Our data thus demonstrate a daily [Cl-]i modulation with complex effects on cortical excitability.

Publication metadata

Author(s): Pracucci E, Graham RT, Alberio L, Nardi G, Cozzolino O, Pillai V, Pasquini G, Saieva L, Walsh D, Landi S, Zhang J, Trevelyan AJ, Ratto G-M

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2023

Volume: 14

Issue: 1

Online publication date: 04/11/2023

Acceptance date: 19/10/2023

ISSN (electronic): 2041-1723

Publisher: Nature Research


DOI: 10.1038/s41467-023-42711-7


Altmetrics provided by Altmetric