ArticleNature communications2016
Cl-out is a novel cooperative optogenetic tool for extruding chloride from neurons.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Chloride Homeostasis Failure in Human Disease: KCC2/NKCC1 Microdomain Dysfunction as a Driver of Cortical Network Collapse.International journal of molecular sciences · 2026Review
- Electrophysiologically Targeted Biopsies Reveal the Transcriptional Landscape of Focal Epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Sleep-wake-related changes in intracellular chloride regulate plasticity at glutamatergic cortical synapses.Current biology : CB · 2025Article
- Optogenetic Determination of Dynamic and Cell-Type-Specific Inhibitory Reversal Potentials.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability.Nature communications · 2023Article
- Inhibition of Dopamine Neurons Prevents Incentive Value Encoding of a Reward Cue: With Revelations from Deep Phenotyping.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Optogenetic stimulation reveals a latent tipping point in cortical networks during ictogenesis.Brain : a journal of neurology · 2023Article
- Closed-loop optogenetic control of the dynamics of neural activity in non-human primates.Nature biomedical engineering · 2023Article
- In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.CNS neuroscience & therapeutics · 2023Article
- Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Rhodopsins: An Excitingly Versatile Protein Species for Research, Development and Creative Engineering.Frontiers in chemistry · 2022Review
- Excitatory GABAergic signalling is associated with benzodiazepine resistance in status epilepticus.Brain : a journal of neurology · 2019Article
- Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Transient ischemia facilitates neuronal chloride accumulation and severity of seizures.Annals of clinical and translational neurology · 2018Article
- Hippocampal GABAergic Inhibitory Interneurons.Physiological reviews · 2017Review
- Review
- Optogenetic Modulation of Intracellular Signalling and Transcription: Focus on Neuronal Plasticity.Journal of experimental neuroscience · 2017Review
- When a Good Cop Turns Bad: The Pro-Ictal Action of Parvalbumin Expressing Interneurons During Seizures.Epilepsy currentsArticle
- Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chloride regulation affects brain function in many ways, for instance, by dictating the GABAergic reversal potential, and thereby influencing neuronal excitability and spike timing. Consistent with this, there is increasing evidence implicating chloride in a range of neurological conditions. Investigations about these conditions, though, are made difficult by the limited range of tools available to manipulate chloride levels. In particular, there has been no way to actively remove chloride from neurons; we now describe an optogenetic strategy, 'Cl-out', to do exactly this. Cl-out achieves its effect by the cooperative action of two different component opsins: the proton pump, Archaerhodopsin and a chloride channel opsin. The removal of chloride happens when both are activated together, using Archaerhodopsin as an optical voltage clamp to provide the driving force for chloride removal through the concurrently opened, chloride channels. We further show that this novel optogenetic strategy can reverse an in vitro epileptogenic phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.