A fresh look at cortical dopamine D2 receptor expressing neurons

The dopamine D2 receptor (DRD2) remains the principal target of antipsychotic drugs used for the management of schizophrenia and other psychotic disorders. This receptor is highly expressed within the basal ganglia, more specifically the striatal caudate nucleus and the nucleus accumbens. The general functions, signaling and behavioral contributions of striatal DRD2 are well understood. However, the study of cortical DRD2 expression and functions has for the most part been restricted to a subset of pyramidal neurons and interneurons (e.g. parvalbumine positive) of the pre frontal cortex where DRD2 regulated local circuits are believed to contribute to the regulation of emotional and cognitive functions. The further investigations of cortical DRD2 functions have been hindered by relatively low receptor expression and the sensitivity of detection methods. Here we report recent findings by our group using high sensitivity approaches to map cortical DRD2 expression. Results from these investigations revealed different scales of heterogeneity within DRD2 expressing neurons. These variations affected the types of neurons expressing DRD2 as well as the co-expression of DRD2 with other receptors across several cortical regions. Furthermore several cortical regions showing higher clusters of DRD2 expressing neurons are involved in the regulation of emotional, cognitive and sensory functions that can be involved in the expression of psychotic symptoms. These findings underscore the need for a reexamination of cortical DRD2 mediated synaptic plasticity in the context of schizophrenia and other psychotic disorders.