The zebrafish cerebellar neural circuits are involved in orienting behavior.

Abstract

Deficits in social behavior are found in neurodevelopmental disorders, including autism spectrum disorders (ASDs). Since abnormalities in cerebellar morphology and function are observed in ASD patients, the cerebellum is thought to play a role in social behavior. However, it remains unknown whether the cerebellum is involved in social behavior in other animals and how cerebellar circuits control social behavior. To address this issue, we employed zebrafish stereotyped orienting behavior as a model of social behaviors, in which a pair of adult zebrafish in two separate tanks approach each other, with one swimming at synchronized angles (orienting angles) with the other. We harnessed transgenic zebrafish that express botulinum toxin, which inhibits the release of neurotransmitters, in either granule cells or Purkinje cells, and zebrafish mutants of reelin, which is involved in the positioning of cerebellar neurons, including Purkinje cells. These zebrafish, deficient in the function or formation of cerebellar neural circuits, showed a significantly shorter period of orienting behavior compared to their control siblings. We found an increase in c-fos and egr1 expression in the cerebellum after the orienting behavior. These results suggest that zebrafish cerebellar circuits play an important role in social orienting behavior.Significance Statement Abnormalities in cerebellar morphology and function are often observed in ASD patients. We describe the roles of cerebellar neural circuitry in social behavior using stereotyped orienting behavior in zebrafish, in which a pair of zebrafish in two separate tanks approach each other and show synchronous swimming. Neurotoxin-mediated inhibition of cerebellar neurons or mutations of the reelin gene, which is required for proper formation of cerebellar neural circuits, shortened the period of the orienting behavior. Furthermore, we found activation of the cerebellum in response to the orienting behavior. Our findings suggest that studies of zebrafish cerebellar neural circuits may provide a model for studying abnormalities in social behaviors, such as those seen in ASD.