PUBLICATION
Kalium channelrhodopsins effectively inhibit neurons
- Authors
- Ott, S., Xu, S., Lee, N., Hong, I., Anns, J., Suresh, D.D., Zhang, Z., Zhang, X., Harion, R., Ye, W., Chandramouli, V., Jesuthasan, S., Saheki, Y., Claridge-Chang, A.
- ID
- ZDB-PUB-240425-15
- Date
- 2024
- Source
- Nature communications 15: 34803480 (Journal)
- Registered Authors
- Jesuthasan, Suresh
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Behavior, Animal
- Caenorhabditis elegans*/genetics
- Channelrhodopsins/genetics
- Channelrhodopsins/metabolism
- Chlorides/metabolism
- Drosophila
- Drosophila melanogaster
- HEK293 Cells
- Humans
- Neurons*/metabolism
- Neurons*/physiology
- Optogenetics*/methods
- Potassium Channels/genetics
- Potassium Channels/metabolism
- Zebrafish*
- PubMed
- 38658537 Full text @ Nat. Commun.
Citation
Ott, S., Xu, S., Lee, N., Hong, I., Anns, J., Suresh, D.D., Zhang, Z., Zhang, X., Harion, R., Ye, W., Chandramouli, V., Jesuthasan, S., Saheki, Y., Claridge-Chang, A. (2024) Kalium channelrhodopsins effectively inhibit neurons. Nature communications. 15:34803480.
Abstract
The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity in Drosophila, Caenorhabditis elegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors for in vivo circuit analysis in behaving animals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping