Overexpression of the vesicular acetylcholine transporter disrupts cognitive performance and causes age-dependent locomotion decline in Drosophila.
Age Factors
Animals
Carrier Proteins
/ metabolism
Central Nervous System
/ metabolism
Cognition
/ physiology
Drosophila
/ metabolism
Learning
/ physiology
Locomotion
/ physiology
Membrane Transport Proteins
/ metabolism
Synaptic Transmission
/ physiology
Vesicular Acetylcholine Transport Proteins
/ metabolism
Vesicular Transport Proteins
/ metabolism
Journal
Molecular and cellular neurosciences
ISSN: 1095-9327
Titre abrégé: Mol Cell Neurosci
Pays: United States
ID NLM: 9100095
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
05
04
2019
revised:
14
03
2020
accepted:
22
03
2020
pubmed:
29
3
2020
medline:
4
3
2021
entrez:
29
3
2020
Statut:
ppublish
Résumé
Acetylcholinergic (ACh) neurotransmission is essential for key organismal functions such as locomotion and cognition. However, the mechanism through which ACh is regulated in the central nervous system is not fully understood. The vesicular acetylcholine transporter (VAChT) mediates the packaging and transport of ACh for exocytotic release and is a critical component of the ACh release machinery. Yet its precise role in the maintenance of cholinergic tone remains a subject of active investigation. Here we use the overexpression of VAChT as a tool to investigate the role of changes in ACh exocytosis on the regulation of synaptic activity and its downstream consequences. We measured the effect of an increase in VAChT expression on locomotion and cognitive performance as well as on organismal survival across the lifespan. We report the surprising finding that increased VAChT expression results in a significantly shorter lifespan in comparison to control flies. Moreover, constructs overexpressing VAChT demonstrate an age-dependent decrease in locomotion performance. Importantly, we report clear deficits in learning and memory which we measured through a courtship conditioning assay. Together, these data provide evidence for the adverse effects of overexpression of the vesicular acetylcholine transporter in the maintenance of normal behavioral abilities in Drosophila and demonstrates for the first time a role for ACh in the regulation of organismal survival.
Identifiants
pubmed: 32217162
pii: S1044-7431(19)30063-6
doi: 10.1016/j.mcn.2020.103483
pmc: PMC7292787
mid: NIHMS1581706
pii:
doi:
Substances chimiques
Carrier Proteins
0
Membrane Transport Proteins
0
Vesicular Acetylcholine Transport Proteins
0
Vesicular Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
103483Subventions
Organisme : NIA NIH HHS
ID : K01 AG049055
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103653
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM122722
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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