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 Merre, Marcus Saarinen, Katarina Tiklova, Behzad Yaghmaeian Salmani, Linda Gillberg, Xiaoqun Zhang, Karima Chergui, Marie Carlén, Stefania Giacomello, Bastian Hengerer, Thomas Perlmann and Per Svenningsson
Additional contact information
Ioannis Mantas: Karolinska Institutet
Ivana Flais: Karolinska Institutet
Yuvarani Masarapu: KTH Royal Institute of Technology
Tudor Ionescu: Boehringer Ingelheim Pharma GmbH & Co. KG
Solène Frapard: KTH Royal Institute of Technology
Felix Jung: Karolinska Institutet
Pierre Merre: Karolinska Institutet
Marcus Saarinen: Karolinska Institutet
Katarina Tiklova: Karolinska Institutet
Behzad Yaghmaeian Salmani: Karolinska Institutet
Linda Gillberg: Karolinska Institutet
Xiaoqun Zhang: Karolinska Institutet
Karima Chergui: Karolinska Institutet
Marie Carlén: Karolinska Institutet
Stefania Giacomello: KTH Royal Institute of Technology
Bastian Hengerer: Boehringer Ingelheim Pharma GmbH & Co. KG
Thomas Perlmann: Karolinska Institutet
Per Svenningsson: Karolinska Institutet

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52429-9

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