Cerebellum-specific deletion of the GABAAreceptor δ subunit alters anxiety-like, social and maternal behaviors without affecting motor performance

Abstract

AbstractGABAAreceptors containing the δGABAAsubunit (δGABAARs) are involved in many physiological and pathophysiological processes, such as sleep, pain, stress, anxiety-related behaviors, and postpartum depression. These extrasynaptically located, high affinity and slowly desensitizing receptors mediate tonic inhibition throughout the brain, including in granule cells (GCs) of the cerebellar input layer. However, the extent to which δGABAARs control the excitability of the cerebellar input layer and ultimately regulate behavior is unknown. We therefore deleted δGABAAsubunits specifically from GCs and determined the behavioral consequences in mice. Deletion reduced tonic inhibition and increased input layer excitability, but remarkably, did not affect either locomotion or motor learning. Unexpectedly, δGABAAdeletion heightened anxiety-like behaviors, and caused female-specific alterations in social and maternal behavior. Our findings establish that the cerebellar input layer is critical for regulating diverse behaviors that are relevant to psychiatric and neurodevelopmental disorders but were previously not associated with the cerebellum.