A research study describes how dopamine modulates social behavior through its action on D2 receptors (D2R) in the cerebellum. The cerebellum is essential for higher cognitive functions, including social behavior, but also contributes to it. Researchers from Inserm Montpellier University (France), Institut de Neurosciences UAB (Spain) and University of Lausanne (Switzerland) uncovered a new role for dopamine as a modulator of social behavior in the mouse cerebellum.
These new findings pave the way to determine whether socially related mental disorders are also associated with altered expression of dopamine receptors in specific cerebellar cell types. Dopamine (DA) neurons are a major component of the brain reward system. By encoding motivational value and prominence, they tightly control motivation, emotional states, and social interactions.
Although the regulation of these processes has largely been ascribed to neural circuits embedded in limbic regions, recent evidence indicates that the cerebellum, a region primarily involved in motor control, is also involved in higher cognitive functions, including social behavior. can contribute. However, whether cerebellar dopamine signaling may participate in the modulation of these functions remained unexplored. By combining cell type-specific transcriptomics, immunofluorescence analysis and 3D imaging, the researchers first demonstrated the presence of dopamine D2 receptors (D2Rs) in Purkinje cells (PCs), the output neurons of the cerebellar cortex. Using patch-clamp recordings, they were able to show D2R modulated synaptic excitability on the PC. “This first set of results was already deterministic for us, as they revealed that D2Rs were present in the cerebellum and, despite their low expression level, they were functional,” said Dr Emmanuel Valgent, director of research at Inserm (France). highlights, and coordinators of the study.
Researchers then studied their functions. Using a genetic approach to selectively invalidate or overexpress the D2R in PC, they analyzed the impact of these changes on motor and non-motor cerebellar functions. “We have uncovered an unexpected causal link between PC D2R expression levels in the cerebellum, the cruciate I/II lobules, and the modulation of social behaviors. Decreasing the expression of this specific dopamine receptor also affected the sociality of the mice.” as their preference for social novelty, while their coordination and motor functions remained unaffected” says Dr Marie-Curie researcher in the Mitochondrial Neuropathology Research Group at INC-UAB. Laura Katando and first author of the article explains.
This study is a first step towards a better understanding of the role of dopamine in the cerebellum and underlying psychiatric disorders such as schizophrenia, ADHD and anxiety disorders, which all have normal DA signaling and altered social behavior. (ANI)
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