Claustral cell identity is determined by Nurr1 and regulates hallucinogenic-like states

Nurr1 is a transcription factor, which is highly enriched in the claustrum (CLA), an enigmatic brain region that has been hypothesized to control hallucinations. Here, by using virus mediated deletion in conditional gene-targeted mice, we investigated the role of Nurr1 in CLA. These mice exhibited loss of the CLA transcriptional identity. To further study the role of Nurr1 in CLA we designed conditional Nurr1 knock out mice under D1 receptor promoter (D1R-Nurr1cKO). Accordingly, these mice showed similar results in CLA marker gene expression with the viral-targeted strategy. Moreover, D1R-Nurr1cKO mice exhibited loss of hallucinogen receptor signaling in CLA. Functional ultrasound imaging showed that hallucinogenic serotoninergic and opioidergic receptor agonists increased functional connectivity between prefrontal cortex and somatomotor regions in control mice but not in D1R-Nurr1cKO. Conclusively, we demonstrate that Nurr1 loss ablates CLA cell identity, which may affect hallucinogenic-like states. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells at two time points.