Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 36, Pages 18060-18067Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1908126116
Keywords
autism; conditional knockout; interneurons; behavior; 4E-BP2
Categories
Funding
- Brain Canada/FNC grant
- Canadian Institutes of Health Research foundation [FDN-148423]
- Howard Hughes Medical Institute Distinguished Researcher [55007654]
- Brain & Behaviour Research Foundation
- FRAXA Research Foundation/Fragile X Research Foundation of Canada Fellowship
- Richard Tomlinson Doctoral Fellowship
- Healthy Brains for Healthy Lives Fellowship (Canada First Research Excellence Fund)
Ask authors/readers for more resources
Translational control plays a key role in regulation of neuronal activity and behavior. Deletion of the translational repressor 4E-BP2 in mice alters excitatory and inhibitory synaptic functions, engendering autistic-like behaviors. The contribution of 4E-BP2-dependent translational control in excitatory and inhibitory neurons and astrocytic cells to these behaviors remains unknown. To investigate this, we generated cell-type-specific conditional 4E-BP2 knockout mice and tested them for the salient features of autism, including repetitive stereotyped behaviors (self-grooming and marble burying), sociability (3-chamber social and direct social interaction tests), and communication (ultrasonic vocalizations in pups). We found that deletion of 4E-BP2 in GABAergic inhibitory neurons, defined by Gad2, resulted in impairments in social interaction and vocal communication. In contrast, deletion of 4E-BP2 in forebrain glutamatergic excitatory neurons, defined by Camk2a, or in astrocytes, defined by Gfap, failed to cause autistic-like behavioral abnormalities. Taken together, we provide evidence for an inhibitory-cell-specific role of 4E-BP2 in engendering autism-related behaviors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available