Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output
Abstract
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 (http://crcns.org/data-sets/brainstem/pag-1), under the doi: 10.6080/K0R49P0V. Users must first create a free account (https://crcns.org/register) before they can download the datasets from the site.
Article and author information
Author details
Funding
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.
Reviewing Editor
- Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States
Ethics
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.
Version history
- Received: January 9, 2019
- Accepted: March 4, 2019
- Accepted Manuscript published: March 7, 2019 (version 1)
- Version of Record published: March 26, 2019 (version 2)
Copyright
© 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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