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Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum

Author

Listed:
  • Shannon L. Wolfman

    (University of Chicago)

  • Daniel F. Gill

    (University of Chicago)

  • Fili Bogdanic

    (University of Chicago)

  • Katie Long

    (University of Chicago)

  • Ream Al-Hasani

    (Washington University School of Medicine)

  • Jordan G. McCall

    (Washington University School of Medicine
    Washington University Pain Center
    Washington University School of Medicine)

  • Michael R. Bruchas

    (Washington University Pain Center
    Washington University School of Medicine)

  • Daniel S. McGehee

    (University of Chicago
    University of Chicago)

Abstract

Nicotine use can lead to dependence through complex processes that are regulated by both its rewarding and aversive effects. Recent studies show that aversive nicotine doses activate excitatory inputs to the interpeduncular nucleus (IPN) from the medial habenula (MHb), but the downstream targets of the IPN that mediate aversion are unknown. Here we show that IPN projections to the laterodorsal tegmentum (LDTg) are GABAergic using optogenetics in tissue slices from mouse brain. Selective stimulation of these IPN axon terminals in LDTg in vivo elicits avoidance behavior, suggesting that these projections contribute to aversion. Nicotine modulates these synapses in a concentration-dependent manner, with strong enhancement only seen at higher concentrations that elicit aversive responses in behavioral tests. Optogenetic inhibition of the IPN–LDTg connection blocks nicotine conditioned place aversion, suggesting that the IPN–LDTg connection is a critical part of the circuitry that mediates the aversive effects of nicotine.

Suggested Citation

  • Shannon L. Wolfman & Daniel F. Gill & Fili Bogdanic & Katie Long & Ream Al-Hasani & Jordan G. McCall & Michael R. Bruchas & Daniel S. McGehee, 2018. "Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04654-2
    DOI: 10.1038/s41467-018-04654-2
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    Cited by:

    1. Susanna Molas & Timothy G. Freels & Rubing Zhao-Shea & Timothy Lee & Pablo Gimenez-Gomez & Melanie Barbini & Gilles E. Martin & Andrew R. Tapper, 2024. "Dopamine control of social novelty preference is constrained by an interpeduncular-tegmentum circuit," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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