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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

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Abstract

© 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

URL: https://doi.org/10.1038/s41467-023-42711-7

DOI: 10.1038/s41467-023-42711-7

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