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Contrôle du réseau périneuronal par l’activité des interneurones à décharge rapide exprimant la parvalbumine

Abstract : The closure of the highly plastic period, called critical period, is concomitant with the accumulation of a specialized extracellular matrix, the perineuronal net (PNN), around fast-spiking inhibitory interneurons that express parvalbumin (FS-PV). The PNN limits the plasticity of cortical maps in the adult, and its enzymatic digestion allows the reopening of cortical maps plasticity. The specific inhibition of FS-PV interneurons, reinstates high cortical plasticity, which may be linked to changes in the PNN. To date, the link between FS-PV cell activity and the regulation of PNN density in the adult remains unexplored. My thesis project aims to determine (i) what are the effects of the manipulation of FS-PV activity on PNN density in the primary visual cortex of adult mice and (ii) if FS-PV interneurons express keys proteins to remodel the PNN. We found that targeted chemogenetic inhibition of FS-PV interneurons or of neighboring pyramidal cells strongly reduces the PNN in adult mice. Overexcitation of the network does not affect the PNN. These results combined with electrophysiological characterization performed using patch-clamp or using EEG recordings, show that network disinhibition is not the trigger of PNN regression. Interestingly, our results suggest that each FS-PV cells is able to regulate its own PNN supported by our results of the expression pattern of PNN-related genes found in FS-PV interneurons. To conclude, our results show that a decrease of FS-PV cells activity, directly or through inhibition of nearby pyramidal cells, reduces PNN density in the adult. These results are innovative and deepen our understanding of PNN regulation mechanisms in adults.
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Gabrielle Devienne. Contrôle du réseau périneuronal par l’activité des interneurones à décharge rapide exprimant la parvalbumine. Neurosciences [q-bio.NC]. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS474⟩. ⟨tel-02931837⟩

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