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Genetically encoded sensors for Chloride concentration

Lookup NU author(s): Professor Andrew Trevelyan


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© 2022. Insights into chloride regulation in neurons have come slowly, but they are likely to be critical for our understanding of how the brain works. The reason is that the intracellular Cl- level ([Cl-]i) is the key determinant of synaptic inhibitory function, and this in turn dictates all manner of neuronal network function. The true impact on the network will only be apparent, however, if Cl- is measured at many locations at once (multiple neurons, and also across the subcellular compartments of single neurons), which realistically, can only be achieved using imaging. The development of genetically-encoded anion biosensors (GABs) brings the additional benefit that Cl- imaging may be done in identified cell-classes and hopefully in subcellular compartments. Here, we describe the historical background and motivation behind the development of these sensors and how they have been used so far. There are, however, still major limitations for their use, the most important being the fact that all GABs are sensitive to both pH and Cl-. Disambiguating the two signals has proved a major challenge, but there are potential solutions; notable among these is ClopHensor, which has now been developed for in vivo measurements of both ion species. We also speculate on how these biosensors may yet be improved, and how this could advance our understanding of Cl- regulation and its impact on brain function.

Publication metadata

Author(s): Lodovichi C, Ratto GM, Trevelyan AJ, Arosio D

Publication type: Review

Publication status: Published

Journal: Journal of Neuroscience Methods

Year: 2022

Volume: 368

Print publication date: 15/02/2022

Online publication date: 22/12/2021

Acceptance date: 18/12/2021

ISSN (print): 0165-0270

ISSN (electronic): 1872-678X

Publisher: Elsevier B.V.


DOI: 10.1016/j.jneumeth.2021.109455