Claustral neurons projecting to frontal cortex restrict opioid consumption

Anna Terem, Yonatan Fatal, Noa Peretz-Rivlin, Hagit Turm, Shahar Shohat Koren, Danny Kitsberg, Reut Ashwal-Fluss, Diptendu Mukherjee, Naomi Habib, Ami Citri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The synthetic opioid fentanyl is a major contributor to the current opioid addiction crisis. We report that claustral neurons projecting to the frontal cortex limit oral fentanyl self-administration in mice. We found that fentanyl transcriptionally activates frontal-projecting claustrum neurons. These neurons also exhibit a unique suppression of Ca2+ activity upon initiation of bouts of fentanyl consumption. Optogenetic stimulation of frontal-projecting claustral neurons, intervening in this suppression, decreased bouts of fentanyl consumption. In contrast, constitutive inhibition of frontal-projecting claustral neurons in the context of a novel, group-housed self-administration procedure increased fentanyl bout consumption. This same manipulation also sensitized conditioned-place preference for fentanyl and enhanced the representation of fentanyl experience in the frontal cortex. Together, our results indicate that claustrum neurons exert inhibitory control over frontal cortical neurons to restrict oral fentanyl intake. Upregulation of activity in the claustro-frontal projection may be a promising strategy for reducing human opioid addiction.

Original languageAmerican English
Pages (from-to)2761-2773.e8
JournalCurrent Biology
Volume33
Issue number13
DOIs
StatePublished - 10 Jul 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • anterior cingulate cortex
  • claustrum
  • conditioned-place preference
  • constitutive silencing
  • fentanyl
  • home-cage behavior
  • neuropixels
  • opioids
  • optogenetics
  • orbitofrontal cortex
  • photometry
  • self-administration
  • transcriptomics

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