Restoring Shank3 in the rostral brainstem of shank3ab-/- zebrafish autism models rescues sensory deficits.

ABSTRACT: People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly exhibit reduced responses to sensory stimuli; yet the changes in brain-wide activity that link these symptoms to mutations in the shank3 gene remain unknown. Here we quantify movement in response to sudden darkness in larvae of two shank3 zebrafish mutant models and show that both models exhibit dampened responses to this stimulus. Using brain-wide activity mapping, we find that shank3^-/- light-sensing brain regions show normal levels of activity while sensorimotor integration and motor regions are less active. Specifically restoring Shank3 function in a sensorimotor nucleus of the rostral brainstem enables the shank3^-/- model to respond like wild-type. In sum, we find that reduced

SUBMITTER: Kozol RA 

PROVIDER: S-EPMC8683502 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature