: 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.

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

Nardi, Gabriele;Pasquini, Giacomo;
2023

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.
2023
Settore BIO/09 - Fisiologia
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Intracellular chloride; epileptiform activity; gabaergic neurons; gaba; sleep; inhibition; PH; phosphorylation; synchronization; hippocampus
   Changing network interactions in models of medically refractory epilepsy
   UK Research and Innovation
   MRC
   MR/R005427/1

   Cl-out: a novel cooperative-optogenetic strategy to control neuronal chloride
   UK Research and Innovation
   BBSRC
   BB/P019854/1

   Intracellular chloride dynamics in autistic brain: a better understanding is needed for tailored cures
   Fondazione Telethon

   Developmental and epileptic encephalopaties: epidemiology, comorbidities, molecular diagnosis, personalized management, and costs analysis
   DECODE-EE
   Regione Toscana
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/136783
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