This image of a mouse cerebellum expressing a fluorescent protein in Purkinje cells expressing dopamine D2 receptors. © Emmanuel Valjent, Institute of Functional Genomics (Montpellier).
Located in the back of the skull, the cerebellum is a key brain region for controlling motor functions, but it also contributes to higher cognitive functions, including social behaviors. In a recent study, an international research consortium including scientists from Inserm, the University of Montpellier, the CNRS, the Neurociències Universitat Autònoma de Barcelona (INc-UAB) (Spain) and the University of Lausanne (Switzerland) have discovered how a neurotransmitter in the cerebellum, dopamine, modulates Social behavior through action on a specific dopamine receptor called D2R. Using mouse models and various genetic tools, the researchers showed that changes in D2R levels, in a specific type of cerebellar cell, modulate social communication and preference for social novelty, without affecting motor functions. these results, Published in the newspaper natural neuroscienceIt opens the way for a better understanding of some psychological disorders associated with social communication, such as autism spectrum disorders (ASD), bipolar disorders or schizophrenia.
Dopamine (DA) is the main neurotransmitter in the brain’s reward system, involved in controlling impulses, emotional states, and social interactions. The regulation of these processes depends to a large extent on the activation of the neural integrated circuits in the limbic regions. However, recent evidence suggests that the cerebellum, an area traditionally associated with motor control, may also contribute to higher cognitive functions, including social behaviors.
To go further and better understand the role of the cerebellum, researchers from Inserm, University of Montpellier, CNRS, Institut Neurociències UAB (Spain) and University of Lausanne (Switzerland) highlighted a new role for dopamine in the cerebellum, shown to modulate social behaviors in mice.
By combining transcriptomic analysis Cell-type-specific and immunofluorescence and 3-D imaging analyses, the researchers first demonstrated the presence of a specific type of dopamine receptor (called a D2R) in the main output neurons of the cerebellum, Purkinje cells. Thanks to recordings of neuronal activity, they were able to show that D2Rs modulated the excitation of Purkinje cells.
“This first series of results was really crucial for us, because it revealed that D2Rs were indeed present in the cerebellum, which was not yet clear, and although their expression was low, they were functional. Emmanuel Valgent, director of research at Inserm and coordinator of the study confirms.
Understand the role of dopamine in the cerebellum
The researchers then looked at the function of D2R receptors within these neurons in the cerebellum. Using genetic approaches to selectively decrease or increase the amount of D2R receptors in Purkinje cells, they analyzed the effect of these alterations on motor and non-motor functions of the cerebellum.
Thus, the scientists demonstrated that there is a correlation between the amount of D2R expressed in Purkinje cells and the modulation of social behavior.
“Reducing the expression of this specific dopamine receptor impaired the mice’s ability to socialize as well as their preference for social novelty, while their coordination and motor functions were not affected. Explains Dr. Laura Cutando, a postdoctoral student at Inserm and now a UAB researcher, and first author of the article.
This study is a first step towards a better understanding of the role of dopamine in the cerebellum and the mechanisms underlying psychiatric disorders such as schizophrenia, ADHD and anxiety disorders, which all share common variable levels of dopamine and altered social behaviors.
 Transcription is the analysis of messenger RNA transcribed in a cell, tissue or organism, which makes it possible to determine the expression of genes.
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