Dysfunction of distinct amygdala circuits in a 16p11.2 model of autism The overall goal of this project is to investigate the brain mechanisms underlying the abnormal repetitive behaviors and emotional processing in a genetic model of autism spectrum disorders (ASD), which was developed in mice to mimic a microdeletion on human chromosome 16p11.2, one of the most common genetic variations found in ASD. Besides other symptoms, patients with this deletion show severe repetitive behaviors and anxiety, two frequently comorbid symptoms in ASD. Despite intensive study, the mechanisms underlying the repetitive behaviors in ASD and the high prevalence of comorbidity between ASD and anxiety disorders remain largely unknown. In the proposed study, we plan to approach these questions by investigating the role of distinct amygdala circuits in abnormal habitual behaviors and fear processing in mice heterozygous for a deficiency allele of the region corresponding to the human 16p11.2, named as the 16p11.2 df/+ mice. We will test the hypothesis that dysfunction of distinct amygdala circuits in the 16p11.2 df/+ mice causes abnormal habitual behaviors and impairment in fear processing characteristic of ASD. In order to test this hypothesis, we have devised an integrated strategy that combines molecular genetic tools together with electrophysiological, chemogenetic, and behavioral techniques. Findings from this research program will provide novel insight into the synaptic, cellular, and circuit mechanisms by which dysfunction of distinct amygdala circuits contributes to abnormal behaviors related to ASD.
The neural mechanisms underlying the symptoms in autism remain unclear. In the proposed research program, we will determine how dysfunction of distinct amygdala circuits contribute to the abnormal repetitive behaviors and fear processing in a 16p11.2 model of autism. Findings from this project will have important clinical implications, as abnormal repetitive behaviors and anxiety disorders are frequently comorbid in autism.
| Schiff, Hillary C; Bouhuis, Anna Lien; Yu, Kai et al. (2018) An Insula-Central Amygdala Circuit for Guiding Tastant-Reinforced Choice Behavior. J Neurosci 38:1418-1429 |
| Yu, Kai; Ahrens, Sandra; Zhang, Xian et al. (2017) The central amygdala controls learning in the lateral amygdala. Nat Neurosci 20:1680-1685 |
