Single-cell RNA and electrophysiological profiling of D1+ and D2+ principal neurons of the prefrontal cortex

Dopaminergic modulation of the prefrontal cortex (PFC) circuits is crucial for cognitive processes such as working memory, planning, attention and dysfunction. This system has been linked to cognitive deficits associated with schizophrenia and autism spectrum disorders. Despite its physiological and pathophysiological importance, we are still lacking a clear understanding of the basic principles of dopamine (DA) actions in the PFC. We set out to provide a detailed classification of layer 5 pyramidal neurons mediating the two main streams of DA signaling, namely via DA receptor group 1 (D1) and DA receptor group 2 (D2). To achieve this, we combined electrophysiological whole-cell recordings in acute slices of the prelimbic part (PL) of the medial PFC with single cell RNA sequencing, morphological and immunohistochemical analysis. 15 D1 cells/ 26 D2 cells for the WT condition and 6 D1 cells and 7 D2 cells for the KO condition (Fmr1-/y mice; this is a mouse model for fragile x syndrome and autism spectrum disorder)