Genetic Labeling Reveals Temporal And Spatial Expression Pattern Of D2 Dopamine Receptor In Rat Brain

The D2 dopamine receptor(Drd2)is GPCR,which is responsible for such crucial processes as voluntary movement,sleep,regulation of food intake,attention,learning,and working memory,and is also implicated in several brain disorders such as schizophrenia,Parkinson’s disease,and drug addiction.Drd2 is also the primary target of both antipsychotics and Parkinson’s disease medications.Although the expression pattern of Drd2 is relatively well known in mouse brain,the temporal and spatial distribution of Drd2 is lesser clear in rat brain due to the lack of Drd2 reporter rat lines,which impede the study of physiological function and pathophysiological roles of Drd2.Here,we used CRISPR/Cas9 techniques to generate and then verified two knockin rat lines: Drd2::Cre and Rosa26::loxp-stop-loxp-tdTomato.By crossing these two lines,we produced Drd2 reporter rats expressing the fluorescence protein tdTomato under the control of the endogenous Drd2 promoter.Using fluorescence imaging and unbiased stereology,we revealed the cellular expression pattern of Drd2 in adult and postnatal rat forebrain.Strikingly,the Drd2 expression pattern differs between Drd2 reporter rats and Drd2 reporter mice generated by BAC transgene in prefrontal cortex and hippocampus.The paper focuses on the expression of Drd2 in olfactory bulb,cortex,hippocampus.These results provide necessary basic information for the study of Drd2 function in rat brain.The Drd2::Cre rats generated here may represent a useful tool to study the function of neuronal populations expressing Drd2.