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Encoding of danger by parabrachial CGRP neurons

Nature volume 555, pages 617622 (29 March 2018) | Download Citation


Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calcium transients in vivo from individual neurons in mice, we show that most CGRPPBN neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). The same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel foods or by an auditory cue that has previously been paired with electrical footshocks. Correspondingly, silencing of CGRPPBN neurons attenuates the expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioural states that limit harm in response to potential threats.

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Research was supported by a fellowship grant from Hope Funds for Cancer Research (C.A.C.), a National Institutes of Health (NIH) training grant (C.W.R., T32DK007247), and an NIH grant (R.D.P., R01-DA24908). Inscopix provided the calcium imaging equipment via their DECODE program. We thank C. de Solages and L. Cardy (Inscopix) for advice regarding calcium imaging, Y. S. Jo for help with conditioning equipment, M. Chiang for maintaining the mouse colony, and S. Han for making the GCaMP6m virus.

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  1. Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA

    • Carlos A. Campos
    • , Anna J. Bowen
    • , Carolyn W. Roman
    •  & Richard D. Palmiter


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C.A.C. designed and conducted the calcium imaging studies. A.J.B. performed the stereotaxic surgeries for loss-of-function studies. C.A.C. and A.J.B. designed and conducted the fear studies. C.A.C. and C.W.R. designed and conducted the itch studies. R.D.P. provided guidance and resources. C.A.C. wrote the manuscript with input from the other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Carlos A. Campos or Richard D. Palmiter.

Reviewer Information Nature thanks C. Alexander and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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    This file contains the detailed statistical analysis.


  1. 1.

    CGRPPBN neurons in anesthetized mice are activated by tail pinch

    This is an unprocessed video file from calcium imaging.

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    CGRPPBN neurons are inhibited before food consumption

    Calcium recording was processed using CNMF, and the fluorescence of each neuron was normalized to its own maximum fluorescence intensity in the video.

  3. 3.

    CGRPPBN neurons are active during exploration of novel, palatable food

    Calcium recording was processed using CNMF, and the fluorescence of each neuron was normalized to its own maximum fluorescence intensity in the video. Video is 2x speed.

  4. 4.

    CGRPPBN neurons are active during exploration of novel marble

    Calcium recording was processed using CNMF, and the fluorescence of each neuron was normalized to its own maximum fluorescence intensity in the video. Video is 2x speed.

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