- Awarded: 2022
- Award Type: Pilot
- Award #: 978953
Motor impairments, from altered coordination to reduced flexibility of movements, are among the core features of autism spectrum disorder (ASD). Growing evidence indicates that communication between the cerebellum and the cerebral cortex is critical for producing coordinated movements, learning motor actions and flexibly adjusting behavior. Despite extensive evidence for cerebellar and cortical alterations in ASD, cortico-cerebellar communication remains relatively unexplored. The goal of this proposal is to understand how cortico-cerebellar communication contributes to features of ASD.
In mouse models of ASD, altered cerebellar and cortical structure or function is often associated with dysfunctional motor control and behavioral inflexibility. Understanding how these phenotypes relate to cortico-cerebellar communication requires the study of cortico-cerebellar dependent behaviors combined with high-density, multi-site neurophysiology in mouse models of ASD. Adam Hantman’s lab has recently established that cortico-cerebellar communication is required to produce dexterous reaching movements in mice1.
The objective of this proposal is to leverage the ability to precisely characterize reaching behaviors while monitoring neural activity across the cortico-cerebellar network in three established genetic mouse models of ASD (Shank3B–, Caspr2– and Ube3am-/p+). The central hypothesis of this project is that disrupted cortico-cerebellar communication underlies impairments in motor control and behavioral flexibility in ASD.