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Nat Commun. 2019 Mar 21;10(1):1318. doi: 10.1038/s41467-019-09262-2.

Autophagy within the mushroom body protects from synapse aging in a non-cell autonomous manner.

Author information

1
Institute for Biology/Genetics, Freie Universität Berlin, Takustr. 6, 14195, Berlin, Germany.
2
NeuroCure, Charité, Charitéplatz 1, 11007, Berlin, Germany.
3
Leibniz Forschungsinstitut Für Molecular Pharmakologie, Campus Berlin-Buch, Robert-Roessle-Str. 10, 13125, Berlin, Germany.
4
Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány, s. 1/C. 6.520, Budapest, H-1117, Hungary.
5
Institute for Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstrasse 50/EG, 8010, Graz, Austria.
6
BioTechMed Graz, 8010, Graz, Austria.
7
Institute for Biology/Genetics, Freie Universität Berlin, Takustr. 6, 14195, Berlin, Germany. stephan.sigrist@fu-berlin.de.
8
NeuroCure, Charité, Charitéplatz 1, 11007, Berlin, Germany. stephan.sigrist@fu-berlin.de.

Abstract

Macroautophagy is an evolutionarily conserved cellular maintenance program, meant to protect the brain from premature aging and neurodegeneration. How neuronal autophagy, usually loosing efficacy with age, intersects with neuronal processes mediating brain maintenance remains to be explored. Here, we show that impairing autophagy in the Drosophila learning center (mushroom body, MB) but not in other brain regions triggered changes normally restricted to aged brains: impaired associative olfactory memory as well as a brain-wide ultrastructural increase of presynaptic active zones (metaplasticity), a state non-compatible with memory formation. Mechanistically, decreasing autophagy within the MBs reduced expression of an NPY-family neuropeptide, and interfering with autocrine NPY signaling of the MBs provoked similar brain-wide metaplastic changes. Our results in an exemplary fashion show that autophagy-regulated signaling emanating from a higher brain integration center can execute high-level control over other brain regions to steer life-strategy decisions such as whether or not to form memories.

PMID:
30899013
PMCID:
PMC6428838
DOI:
10.1038/s41467-019-09262-2
[Indexed for MEDLINE]
Free PMC Article

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