Date: Friday, May 6, 2022
Time: 12:00pm – 1:00pm
Location: Zoom meeting – https://mit.zoom.us/j/94097435062 

Speaker: Emily Hueske, Ph.D.
Affiliation: Research Scientist, Graybiel Laboratory, McGovern Institute for Brain Research, MIT

Talk title: Striosomal circuits underlying repetitive behaviors in ASD model

Abstract: Repetitive or stereotyped behaviors are a cardinal feature of autism spectrum disorder. The Graybiel lab is focused on trying to identify particular circuits in the cortico-striatal-dopaminergic system that might account for the anxiety and stereotypic behaviors exhibited by many individuals on the autism spectrum, with special focus on the striosomal compartment of striatum that directly innervates dopaminergic midbrain neurons. Our previous work demonstrated that the degree of stereotypic behaviors in rats, mice and squirrel monkeys correlates with striosomal predominant expression of cfos. We find evidence of the same in marmoset. We recently published a chemogenetic approach to modulating striosomal or matrix circuit activity, and we are testing the effects of striosomal inhibition in Shank3B KO mice using DeepLabCut- and B-SOID-based pose estimation. Shank3B KO mice show elevated stereotypic behaviors, and we are finding that chemogenetic inhibition of striosomal populations reduces these elevated stereotypies. In order to establish a translational approach to manipulating striosomes, we are capitalizing on our findings from recent snRNA-seq analyses to identify enhancer regions likely to allow targeting of expression to striosomal populations in mouse and marmoset without use of recombinase-based methods. This work would allow chemogenetic modulation of striosomal populations in marmoset models just as we have performed in Shank3B knockout mice.