PUBLICATION
Hyperactive mTORC1 disrupts habenula function and light preference in zebrafish model of Tuberous sclerosis complex
- Authors
- Doszyn, O., Kedra, M., Zmorzynska, J.
- ID
- ZDB-PUB-240701-3
- Date
- 2024
- Source
- iScience 27: 110149110149 (Journal)
- Registered Authors
- Zmorzynska, Justyna
- Keywords
- Molecular neuroscience, Neurogenetics, behavioral neuroscience, neuroscience, sensory neuroscience
- MeSH Terms
- none
- PubMed
- 38947496 Full text @ iScience
Citation
Doszyn, O., Kedra, M., Zmorzynska, J. (2024) Hyperactive mTORC1 disrupts habenula function and light preference in zebrafish model of Tuberous sclerosis complex. iScience. 27:110149110149.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping