Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output.

Kristina M Wright,Michael A Mcdannald

doi:10.7554/elife.45013

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.

Highlights

When confronted with potential harm, an estimate of threat probability must be made and followed by an appropriate fear response
We recorded ventrolateral periaqueductal gray (vlPAG) single-unit activity while rats discriminated between danger, uncertainty and safety
Onset activity reflected an estimate of threat probability, invariant of fear output

Summary

Introduction

When confronted with potential harm, an estimate of threat probability must be made and followed by an appropriate fear response. Some studies suggest that the vlPAG may do more than just trigger a fear response To test this idea, Wright and McDannald trained rats to associate three different 10-second tones with different probabilities of receiving a mild electric shock to the foot. The second group of neurons increased its activity over the course of each tone The activity of this group mainly reflected the degree of threat, and represented the rat’s fear response to a lesser extent. We measured fear output using conditioned suppression of reward seeking (Rescorla, 1968; Bouton and Bolles, 1980) over the entire cue and in one-second cue intervals Using this procedure, we have found that suppression non-linearly scales to shock probability. The non-linear relationship between behavior and shock probability permitted us to determine whether vlPAG single-unit activity was better captured by fear output or threat probability

Results

Discussion

Materials and methods

Funding Funder National Institutes of Health