Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability
Enrico Pracucci, R. Graham, Laura Alberio, Gabriele Nardi, Olga Cozzolino, Vinoshene Pillai, Giacomo Pasquini, Luciano Saieva, Darren Walsh, Silvia Landi, Jinwei Zhang, Andrew J. Trevelyan, Gian Michele Ratto
Abstract
Abstract 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.