chloride regulation
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2021 ◽  
Author(s):  
Hannah Alfonsa ◽  
Paul Brodersen ◽  
Sarah Newey ◽  
Tomoko Yamagata ◽  
Marios C Panayi ◽  
...  

Continuous periods of wakefulness are associated with reduced performance levels due to the build-up of sleep pressure in active regions of the brain. These effects manifest as use-dependent changes in cortical network activity and the mechanisms underlying these changes represent targets for overcoming the cognitive effects of tiredness. Here we reveal a central role for intraneuronal chloride levels, which increase in a use-dependent manner during waking, and reduce the strength of local synaptic inhibition in mouse cortex. Activity-dependent increases in chloride account for spatial and temporal features of sleep pressure, they underlie cortical network oscillations in the sleep-deprived state, and targeting chloride regulation in cortex can rescue performance levels when tired. These findings provide a missing link between sleep-wake history, synaptic transmission and cortical dynamics.


2019 ◽  
Author(s):  
Yo Otsu ◽  
Florian Donneger ◽  
Eric J Schwartz ◽  
Jean Christophe Poncer

AbstractTransmembrane chloride gradients govern the efficacy and polarity of GABA signaling in neurons and are usually maintained by the activity of cation chloride cotransporters, such as KCC2 and NKCC1. Whereas their role is well established in cortical principal neurons, it remains poorly documented in GABAergic interneurons. We used complementary electrophysiological approaches to compare the effects of GABAAR activation in adult mouse hippocampal parvalbumin interneurons (PV INs) and pyramidal cells (PCs). Loose cell attached, tight-seal and gramicidin-perforated patch recordings all show GABAAR-mediated transmission is slightly depolarizing and yet inhibitory in both PV INs and PCs. Focal GABA uncaging in whole-cell recordings reveal that KCC2 and NKCC1 are functional in both PV INs and PCs but differentially contribute to transmembrane chloride gradients in their soma and dendrites. Blocking KCC2 function depolarizes the reversal potential of GABAAR-mediated currents in PV INs and PCs, often beyond firing threshold, showing KCC2 is essential to maintain the inhibitory effect of GABAARs. Finally, we show that repetitive 10 Hz activation of GABAARs in both PV INs and PCs leads to a progressive decline of the postsynaptic response independently of the ion flux direction or KCC2 function. This suggests intraneuronal chloride buildup may not predominantly contribute to activity-dependent plasticity of GABAergic synapses in this frequency range. Altogether our data demonstrate similar mechanisms of chloride regulation in mouse hippocampal PV INs and PCs and suggest KCC2 downregulation in the pathology may affect the valence of GABA signaling in both cell types.Key point summaryCation-chloride cotransporters (CCCs) play a critical role in controlling the efficacy and polarity of GABAA receptor (GABAAR)-mediated transmission in the brain, yet their expression and function in GABAergic interneurons has been overlooked.We compared the polarity of GABA signaling and the function of CCCs in mouse hippocampal pyramidal neurons and parvalbumin-expressing interneurons.Under resting conditions, GABAAR activation was mostly depolarizing and yet inhibitory in both cell types. KCC2 blockade further depolarized the reversal potential of GABAAR-mediated currents often above action potential threshold.However, during repetitive GABAAR activation, the postsynaptic response declined independently of the ion flux direction or KCC2 function, suggesting intracellular chloride buildup is not responsible for this form of plasticity.Our data demonstrate similar mechanisms of chloride regulation in mouse hippocampal pyramidal neurons and parvalbumin interneurons.


2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Kirthikaa Balapattabi ◽  
George E Farmer ◽  
Joel T Little ◽  
Martha E Bachelor ◽  
J. Thomas Cunningham

2017 ◽  
Vol 37 (22) ◽  
pp. 5447-5462 ◽  
Author(s):  
Rebecca Wright ◽  
Sarah E. Newey ◽  
Andrei Ilie ◽  
Winnie Wefelmeyer ◽  
Joseph V. Raimondo ◽  
...  

Neuron ◽  
2016 ◽  
Vol 89 (6) ◽  
pp. 1157-1172 ◽  
Author(s):  
Nicolas Doyon ◽  
Laurent Vinay ◽  
Steven A. Prescott ◽  
Yves De Koninck

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Wang Yi‐Fang ◽  
Ruo‐Dong Chen ◽  
Jia‐Jiun Yan ◽  
Pung‐Pung Hwang

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