Claustrum and dorsal endopiriform cortex complex cell-identity is determined by Nurr1 and regulates hallucinogenic-like states in mice

Claustrum and dorsal endopiriform cortex complex (CLA) cell identity depends on the transcription factor Nurr1, and Nurr1 loss shifts brain activity in ways consistent with hallucinogenic-like states in mice. Using conditional gene-targeted mice that delete Nurr1 in CLA neurons, the study finds that CLA neurons remain structurally intact, but their distinctive gene expression program is abolished. After Nurr1 deletion, expression of hallucinogen-related receptor signaling components in CLA is lost, indicating Nurr1 is upstream of a functional hallucinogen receptor landscape. Across measures of neural dynamics, Nurr1-ablated mice show altered responses to hallucinogen receptor agonists, including changes in functional connectivity between prefrontal and sensorimotor cortices. The authors combine functional ultrasound and Neuropixel electrophysiology to link altered CLA receptor signaling and circuit connectivity to hallucinogenic-like changes, suggesting Nurr1-targeted approaches for studying CLA function under hallucinogen-linked states.