A core feature of autism is the expression of repetitive and ritualized behaviors characterized by profound invariability and inflexibility. Autism is also frequently comorbid with anxiety disorders. Despite intensive study, the mechanisms underlying the repetitive and ritualized behavior in autism and the high prevalence of comorbidity between autism and anxiety disorders remain largely unknown.
Previous studies suggest that amygdala dysfunction may contribute to the pathogenesis of autism. Notably, the central amygdala (CeA) has been implicated in both emotional regulation and the establishment of habit, a behavioral strategy that is inflexible and is independent of the outcome of action. Thus, the CeA represents a node at which the emotion circuit and the habit circuit intersect. Nevertheless, it is unclear whether dysfunction of the CeA is responsible for the abnormal habitual behaviors and the frequently associated anxiety symptoms in autism.
In the proposed study, Bo Li and his team at Cold Spring Laboratory plan to address this question by investigating the role of the CeA in abnormal habit formation and anxiety-related behavior in 16p11.2 df/+ mice. These mice are heterozygous for a deficiency (df) allele of the region corresponding to human chromosome region 16p11.2. The mice show stereotyped and habitual behaviors that are reminiscent of the repetitive and ritualized behaviors in autism. The researchers will test the central hypothesis that CeA dysfunction in these mice causes both abnormal habitual behaviors and enhanced anxiety.
The proposed research will establish a framework for future research into the mechanisms underlying both the core and comorbid symptoms of autism, and will ultimately guide the development of novel and effective therapeutics.
