Aberrant outputs of cerebellar nuclei and targeted rescue of social deficits in an autism mouse model.
- Author:
Xin-Yu CAI
1
;
Xin-Tai WANG
2
;
Jing-Wen GUO
1
;
Fang-Xiao XU
3
;
Kuang-Yi MA
3
;
Zhao-Xiang WANG
4
;
Yue ZHAO
3
;
Wei XIE
5
;
Martijn SCHONEWILLE
6
;
Chris DE ZEEUW
6
;
Wei CHEN
3
;
Ying SHEN
1
Author Information
- Publication Type:Journal Article
- Keywords: autism; cerebellum; large-scale tracing; midbrain; thalamus
- MeSH: Animals; Mice; Disease Models, Animal; Cerebellar Nuclei; Autistic Disorder/pathology*; Neurons/metabolism*; Mutation; Nerve Tissue Proteins/metabolism*; Male; Membrane Proteins; Cell Adhesion Molecules, Neuronal
- From: Protein & Cell 2024;15(12):872-888
- CountryChina
- Language:English
- Abstract: The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
