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bioRxiv · 10.1101/2020.05.29.122432

Spatiotemporal chloride dynamics in hypothalamic CRHPVN neurons

Lanz, A. J.·Gordon, G. R.·Bains, J. S.
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Abstract

Chloride (Cl-) dynamics shape inhibitory neurotransmission in the brain. In the hypothalamus, GABA signalling onto corticotropin-releasing hormone (CRHPVN) neurons can switch from inhibitory to excitatory during stress. Although Cl- fluctuations mediate this stress-dependent shift in GABA signalling, the underlying Cl- dynamics are poorly understood. Here, using a novel optogenetic strategy to load intracellular Cl- using halorhodopsin, we demonstrate that KCC2 rapidly restores Cl- setpoints in CRHPVN neurons from naive animals, but that this process is slowed following stress. Further, we report that somatic Cl- homeostasis remains intact after stress. Our results strongly support the idea that KCC2 functions primarily to maintain Cl- setpoints and that inhibitory synapses onto dendritic and somatic compartments of CRHPVN neurons are differentially regulated during stress.

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Lanz, A. J., Gordon, G. R., Bains, J. S.. 2020-05-30. Spatiotemporal chloride dynamics in hypothalamic CRHPVN neurons. https://doi.org/10.1101/2020.05.29.122432

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