Using SuperClomeleon to Measure Changes in Intracellular Chloride during Development and after Early Life Stress

Intraneuronal chloride concentrations ([Cl ] ) decrease during development resulting in a shift from depolarizing to hyperpolarizing GABA responses via chloride-permeable GABA receptors. This GABA shift plays a pivotal role in postnatal brain development, and can be strongly influenced by early life...

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Bibliographic Details
Published in:eNeuro 2022-11, Vol.9 (6), p.ENEURO.0416-22.2022
Main Authors: Herstel, Lotte J, Peerboom, Carlijn, Uijtewaal, Sten, Selemangel, Dunya, Karst, Henk, Wierenga, Corette J
Format: Article
Language:English
Subjects:
Animals
Chlorides - metabolism
Female
gamma-Aminobutyric Acid - pharmacology
Male
Mice
Neurons - physiology
New Research
Receptors, GABA-A
Stress, Physiological
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Summary:Intraneuronal chloride concentrations ([Cl ] ) decrease during development resulting in a shift from depolarizing to hyperpolarizing GABA responses via chloride-permeable GABA receptors. This GABA shift plays a pivotal role in postnatal brain development, and can be strongly influenced by early life experience. Here, we assessed the applicability of the recently developed fluorescent SuperClomeleon (SClm) sensor to examine changes in [Cl ] using two-photon microscopy in brain slices. We used SClm mice of both sexes to monitor the developmental decrease in neuronal chloride levels in organotypic hippocampal cultures. We could discern a clear reduction in [Cl ] between day (DIV)3 and DIV9 (equivalent to the second postnatal week ) and a further decrease in some cells until DIV22. In addition, we assessed alterations in [Cl ] in the medial prefrontal cortex (mPFC) of postnatal day (P)9 male SClm mouse pups after early life stress (ELS). ELS was induced by limiting nesting material between P2 and P9. ELS induced a shift toward higher (i.e., immature) chloride levels in layer 2/3 cells in the mPFC. Although conversion from SClm fluorescence to absolute chloride concentrations proved difficult, our study underscores that the SClm sensor is a powerful tool to measure physiological changes in [Cl ] in brain slices.
ISSN:2373-2822
2373-2822
DOI:10.1523/ENEURO.0416-22.2022