Autophagy in parvalbumin interneurons is required for inhibitory transmission and memory via regulation of synaptic proteostasis
| Autor: | Theodora Chalatsi, Laura M.J. Fernandez, Jules Scholler, Laura Batti, Angeliki Kolaxi, Leonardo Restivo, Anita Lüthi, Manuel Mameli, Vassiliki Nikoletopoulou |
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| Rok vydání: | 2022 |
| Zdroj: | Biorxiv bioRxiv |
| DOI: | 10.1101/2022.10.10.511533 |
| Popis: | SummaryWith the emerging role of the autophagic machinery in healthy brain development and aging, there is a pressing need to better characterize its functions in different neuronal populations, providing cellular insight into autophagy-related brain diseases. Here, we generated and characterized mice with conditional ablation ofatg5in GABAergic neurons expressing parvalbumin (PV-atg5KO), mostly comprising fast-spiking interneurons, as well as Purkinje cells in the cerebellum. Using light-sheet microscopy to image PV neurons throughout the brain, we reveal that autophagy is required for the sustenance of Purkinje cells but not of PV-interneurons. Yet, proteomic analysis showed that autophagy deficiency in cortical and hippocampal PV-interneurons alters the proteostasis of key synaptic proteins, as well as the surface expression of glutamate receptor subunits. Consistently, hippocampal autophagy-deficient PV-interneurons exhibit reduced inhibitory neurotransmission andPV-atg5KOmice display excitation-inhibition imbalance in the hippocampus and memory deficits. Our findings demonstrate a neuronal type-specific vulnerability to autophagy deficiency, while also identifying PV-interneurons as cellular substrates where autophagy is required for memory. |
| Databáze: | OpenAIRE |
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