ArticleFrontiers in cellular neuroscience2015
Mild KCC2 Hypofunction Causes Inconspicuous Chloride Dysregulation that Degrades Neural Coding.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Optogenetic Determination of Dynamic and Cell-Type-Specific Inhibitory Reversal Potentials.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- How Merkel cells transduce mechanical stimuli: A biophysical model of Merkel cells.PLoS computational biology · 2023Article
- Unilateral optogenetic kindling of hippocampus leads to more severe impairments of the inhibitory signaling in the contralateral hippocampus.Frontiers in molecular neuroscience · 2023Article
- Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain.Cells · 2022Review
- Computational models reveal how chloride dynamics determine the optimal distribution of inhibitory synapses to minimise dendritic excitability.PLoS computational biology · 2022Article
- Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model.Science signaling · 2021Article
- Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons.PLoS computational biology · 2021Article
- When Are Depolarizing GABAergic Responses Excitatory?Frontiers in molecular neuroscience · 2021Review
- Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells.Frontiers in cellular neuroscience · 2021Review
- NKCC-1 mediated ClScientific reports · 2020Article
- Article
- Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization.Nature communications · 2020Article
- Chloride dynamics alter the input-output properties of neurons.PLoS computational biology · 2020Article
- Interactions between Membrane Resistance, GABA-A Receptor Properties, Bicarbonate Dynamics and ClInternational journal of molecular sciences · 2019Article
- Coincident Activation of Glutamate Receptors Enhances GABAFrontiers in cellular neuroscience · 2019Article
- Tenuous Inhibitory GABAergic Signaling in the Reticular Thalamus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- The H-Reflex as a Biomarker for Spinal Disinhibition in Painful Diabetic Neuropathy.Current diabetes reports · 2018Review
- Reply to The small molecule CLP257 does not modify activity of the KNature medicine · 2017Article
- Pumilio2-deficient mice show a predisposition for epilepsy.Disease models & mechanisms · 2017Article
- Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disinhibition caused by Cl(-) dysregulation is implicated in several neurological disorders. This form of disinhibition, which stems primarily from impaired Cl(-) extrusion through the co-transporter KCC2, is typically identified by a depolarizing shift in GABA reversal potential (E GABA). Here we show, using computer simulations, that intracellular [Cl(-)] exhibits exaggerated fluctuations during transient Cl(-) loads and recovers more slowly to baseline when KCC2 level is even modestly reduced. Using information theory and signal detection theory, we show that increased Cl(-) lability and settling time degrade neural coding. Importantly, these deleterious effects manifest after less KCC2 reduction than needed to produce the gross changes in E GABA required for detection by most experiments, which assess KCC2 function under weak Cl(-) load conditions. By demonstrating the existence and functional consequences of "occult" Cl(-) dysregulation, these results suggest that modest KCC2 hypofunction plays a greater role in neurological disorders than previously believed.
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