Head-fixed recording of sensory learning in autism mouse models

The cerebellum is a brain region that performs multisensory processing to guide movement and cognition. Although autism spectrum disorders are associated with structural abnormalities and deficiencies in the number and appearance of cells in the cerebellum, cerebellar function in autism has not yet been rigorously characterized.

Samuel Wang and his colleagues at Princeton University are studying sensory learning in mouse models of autism. They use a form of associative learning called delay eyeblink conditioning, which measures a mouse’s ability to associate an air puff to the eye (which always evokes a blink) with an auditory tone. Wang’s team works with mice deficient in one of two genes that are expressed strongly in the cerebellum: SHANK3 or CNTNAP2. These genes are associated with autism in humans, and in mice, their alteration or deletion leads to characteristics such as indifference to other mice, abnormal vocalization and behavioral inflexibility. Normal mice learn the eyeblink conditioning after a few sessions, but mice deficient in SHANK3 or CNTNAP2 have more difficulty. Initial experiments point to specific cerebellar dysfunctions, echoing the results of two studies of delay eyeblink conditioning in people with autism¹,².

Wang’s preliminary results provide a critical link between mouse models and the cellular, anatomical and developmental abnormalities seen in the cerebellum of many people with autism. An understanding of autism-related defects in cerebellar circuits could lead to the development of interventions to recover function in children and adults with the disorder. In addition, Wang aims to develop a reliable way to characterize cerebellar circuit defects, which would provide a biomarker for future therapies.