Nature Communications (Sep 2024)

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

  • Ioannis Mantas,
  • Ivana Flais,
  • Yuvarani Masarapu,
  • Tudor Ionescu,
  • Solène Frapard,
  • Felix Jung,
  • Pierre Le Merre,
  • Marcus Saarinen,
  • Katarina Tiklova,
  • Behzad Yaghmaeian Salmani,
  • Linda Gillberg,
  • Xiaoqun Zhang,
  • Karima Chergui,
  • Marie Carlén,
  • Stefania Giacomello,
  • Bastian Hengerer,
  • Thomas Perlmann,
  • Per Svenningsson

DOI
https://doi.org/10.1038/s41467-024-52429-9
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 18

Abstract

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Abstract The Claustrum/dorsal endopiriform cortex complex (CLA) is an enigmatic brain region with extensive glutamatergic projections to multiple cortical areas. The transcription factor Nurr1 is highly expressed in the CLA, but its role in this region is not understood. By using conditional gene-targeted mice, we show that Nurr1 is a crucial regulator of CLA neuron identity. Although CLA neurons remain intact in the absence of Nurr1, the distinctive gene expression pattern in the CLA is abolished. CLA has been hypothesized to control hallucinations, but little is known of how the CLA responds to hallucinogens. After the deletion of Nurr1 in the CLA, both hallucinogen receptor expression and signaling are lost. Furthermore, functional ultrasound and Neuropixel electrophysiological recordings revealed that the hallucinogenic-receptor agonists’ effects on functional connectivity between prefrontal and sensorimotor cortices are altered in Nurr1-ablated mice. Our findings suggest that Nurr1-targeted strategies provide additional avenues for functional studies of the CLA.