Optogenetic Investigation into the Role of Cerebellar Interneurons in Social Behavior

Abstract

Appropriate social behavior is vital for survival and developmental success of humans and animals. Impaired social behavior is a common symptom in mental illness. However, the neural basis underlying social behavior is not well understood. The cerebellum is classically recognized to be involved in motor control, but recently there has been an increasing appreciation of its role in cognitive and social functions. Human neuroimaging and postmortem studies have shown that cerebellar abnormalities, particularly in Purkinje neurons, are associated with neuropsychiatric disorders. Research using animal models suggests dysfunction of Purkinje neurons, which conduct the output from the entire cerebellar cortex, can generate abnormal social behavior. Yet, how the cerebellar dysfunction is transformed to global pathogenesis of social deficits remains unknown. In the cerebellar circuitry, the activity of Purkinje neurons is critically regulated by molecular layer interneurons (MLIs). In this study, we applied an optogenetic approach to selectively manipulate the excitability of MLIs using a mouse line with genetically encoded channelrhodopsin. By developing an optical stimulation protocol, we demonstrated that the cerebellum was critical for social recognition, which provides a mechanistic insight for the cerebellum-mediated neuropsychiatric disorders.