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Hyperactive mTORC1 disrupts habenula function and light preference in zebrafish model of Tuberous sclerosis complex

Authors :
Olga Doszyn
Magdalena Kedra
Justyna Zmorzynska
Source :
iScience, Vol 27, Iss 6, Pp 110149- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Mechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for brain development. Hyperactive mTORC1 is found in autism spectrum disorder (ASD) characterized by atypical reactivity to sensory stimuli, among other symptoms. In Tuberous sclerosis complex (TSC) inactivating mutations in the TSC1 or TSC2 genes result in hyperactivation of the mTORC1 pathway and ASD. Here, we show that lack of light preference of the TSC zebrafish model, tsc2vu242/vu242 is caused by aberrant processing of light stimuli in the left dorsal habenula and tsc2vu242/vu242 fish have impaired function of the left dorsal habenula, in which neurons exhibited higher activity and lacked habituation to the light stimuli. These characteristics were rescued by rapamycin. We thus discovered that hyperactive mTorC1 caused aberrant habenula function resulting in lack of light preference. Our results suggest that mTORC1 hyperactivity contributes to atypical reactivity to sensory stimuli in ASD.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
6
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.09e77ac095f743bcb4f7a0bbcb733a77
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.110149