Located at the back of the skull, the cerebellum is a brain region classically associated with motor control, while recent studies indicate that it also contributes to higher cognitive functions, including social behaviors.
Emmanuel Valjent’s team, in collaboration with the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) (Spain) and the Université de Lausanne (Switzerland), has discovered how the action of a neurotransmitter in the cerebellum, dopamine, modulates social behaviors via an action on specific dopamine receptor called D2R.
The multidisciplinary consortium combined different approaches, mouse models and genetic tools, to provide a cell type-specific transcriptomics analysis, immunohistological and 3D imaging as well as electrophysiological measures that deciphered the role of D2R in the cerebellum. Their results showed that changes in D2R level in Purkinje cells, the principal output neurons of the cerebellum, modify the sociability and the preference for social novelty, without affecting motor functions. As core mechanism, thanks to neuronal activity recordings the researchers were able to show that D2R modulate the excitation of Purkinje cells.
These results, published in Nature Neuroscience, lead the way towards a better understanding of the role of dopamine in the cerebellum, as well as the mechanisms underlying psychiatric disorders linked to sociability, including autism spectrum disorders (ASD), bipolar mood disorders or schizophrenia.
(Right) Viral injection sites in the cerebellum to knock out D2R receptors.
(Left) 3-chamber sociability test showing greater exploration of a novel conspecific vs. an object in mice with D2R knockouts in Purkinje cells.
