Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output

  1. Kristina M Wright  Is a corresponding author
  2. Michael A McDannald  Is a corresponding author
  1. Boston College, United States


Faced with potential harm, individuals must estimate the probability of threat and initiate an appropriate fear response. In the prevailing view, threat probability estimates are relayed to the ventrolateral periaqueductal gray (vlPAG), to organize fear output. A straightforward prediction is that vlPAG single-unit activity reflects fear output, invariant of threat probability. We recorded vlPAG single-unit activity in male, Long Evans rats undergoing fear discrimination. Three 10-s auditory cues predicted unique foot shock probabilities: danger (p = 1.00), uncertainty (p = 0.375) and safety (p = 0.00). Fear output was measured by suppression of reward seeking over the entire cue and in one-second cue intervals. Cued fear non-linearly scaled to threat probability and cue-responsive vlPAG single-units scaled their firing on one of two timescales: at onset or ramping toward shock delivery. VlPAG onset activity reflected threat probability, invariant of fear output, while ramping activity reflected both signals with threat probability prioritized.

Data availability

Single-unit data are publicly available on CRCNS (, under the doi: 10.6080/K0R49P0V. Users must first create a free account ( before they can download the datasets from the site.

The following data sets were generated

Article and author information

Author details

  1. Kristina M Wright

    Department of Psychology, Boston College, Chestnut Hill, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael A McDannald

    Department of Psychology, Boston College, Chestnut Hill, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8525-1260


National Institutes of Health (MH117791)

  • Michael A McDannald

National Institutes of Health (DA034010)

  • Michael A McDannald

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2018-002) of Boston College. All surgery was performed under isofluorane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States

Version history

  1. Received: January 9, 2019
  2. Accepted: March 4, 2019
  3. Accepted Manuscript published: March 7, 2019 (version 1)
  4. Version of Record published: March 26, 2019 (version 2)


© 2019, Wright & McDannald

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Kristina M Wright
  2. Michael A McDannald
Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output
eLife 8:e45013.

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