Objective: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with two core symptoms, namely repetitive stereotyped behaviors and impairments in social interaction. Neuroligin1 (NLG1) is one of synaptic adhesion molecules, which is a high-risk molecule found in individuals with autism. Previous research has shown that NLG1 knockout mice shown excessive self-grooming behavior and deficits in social ability and memory. The lesions of the striatal-basal ganglia circuit are also the key targets for the pathogenesis of many diseases such as Parkinson's disease, Huntington's disease, and autism. Our project aims to investigate how NLG1 in the striatum regulates repetitive stereotyped behavior investigate, which may provide clinical diagnosis and treatment for autistic patients.

Methods: The expression of NLG1 in the striatum was specifically manipulated by different types of viral tools, and behavioral tests were performed 5-6 weeks later. The activity of neurons was detected by in vivo calcium imaging and electrophysiology. Rescue experiments were carried out by optogenetic, DREADDs, and pharmacological methods.

Results: (1) NLG1 decrease in striatum promote restricted and repetitive behaviors. (2) Knocking down NLG1 in dorsal D2-MSN (medium spiny neuron) of striatum induces restricted and repetitive behaviors. (3) Adult restoration of NLG1 expression in D2-MSN of NLG1 knockout mice rescue repetitive and restricted behaviors. (4) The loss of NLG1 in D2-MSN induces an increase in neuronal excitability. (5) Dorsal D2-MSN is excessive activated in NLG1 KO mice, thus inhibiting D2-MSN activity can recue restricted and repetitive behaviors.

Conclusion: The restricted and repetitive behavior of NLG1-deficient mice are caused by excessive activation of dorsal D2-MSN.

Audience Take Away

• Understand current techniques used in basic neurobiology research, including in vivo calcium, optogenetic, DREADDs, and pharmacological
• Be familiar with the current status of autism, including prevalence, risk factors, and treatment options
• Help the audience better understand the heterogeneity and particularity of striatum brain region, which is an important region of ASD patients
• Know the role of NLG1 in autism, and how to design drugs to treat behavioral deficits associated with ASD by the molecular mechanism based on NLG1