Longitudinal functional imaging of VIP interneurons reveals sup-population specific effects of stroke that are rescued with chemogenetic therapy

Mohamad Motaharinia, Kim Gerrow, Roobina Boghozian, Emily White, Sun-Eui Choi, Kerry R. Delaney and Craig E. Brown ()
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Mohamad Motaharinia: Division of Medical Sciences, University of Victoria
Kim Gerrow: Division of Medical Sciences, University of Victoria
Roobina Boghozian: Division of Medical Sciences, University of Victoria
Emily White: Division of Medical Sciences, University of Victoria
Sun-Eui Choi: Division of Medical Sciences, University of Victoria
Kerry R. Delaney: University of Victoria
Craig E. Brown: Division of Medical Sciences, University of Victoria

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Stroke profoundly disrupts cortical excitability which impedes recovery, but how it affects the function of specific inhibitory interneurons, or subpopulations therein, is poorly understood. Interneurons expressing vasoactive intestinal peptide (VIP) represent an intriguing stroke target because they can regulate cortical excitability through disinhibition. Here we chemogenetically augmented VIP interneuron excitability in a murine model of photothrombotic stroke and show that it enhances somatosensory responses and improves recovery of paw function. Using longitudinal calcium imaging, we discovered that stroke primarily disrupts the fidelity (fraction of responsive trials) and predictability of sensory responses within a subset of highly active VIP neurons. Partial recovery of responses occurred largely within these active neurons and was not accompanied by the recruitment of minimally active neurons. Importantly, chemogenetic stimulation preserved sensory response fidelity and predictability in highly active neurons. These findings provide a new depth of understanding into how stroke and prospective therapies (chemogenetics), can influence subpopulations of inhibitory interneurons.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26405-6

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DOI: 10.1038/s41467-021-26405-6

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