Cue-inhibited ventrolateral periaqueductal gray neurons signal fear output and threat probability in male rats.

Kristina M Wright,Thomas C Jhou,Daniel Pimpinelli,Michael A Mcdannald

doi:10.7554/elife.50054

Abstract

The ventrolateral periaqueductal gray (vlPAG) is proposed to mediate fear responses to imminent danger. Previously we reported that vlPAG neurons showing short-latency increases in firing to a danger cue - the presumed neural substrate for fear output - signal threat probability in male rats (Wright et al., 2019). Here, we scrutinize the activity vlPAG neurons that decrease firing to danger. One cue-inhibited population flipped danger activity from early inhibition to late excitation: a poor neural substrate for fear output, but a better substrate for threat timing. A second population showed differential firing with greatest inhibition to danger, less to uncertainty and no inhibition to safety. The pattern of differential firing reflected the pattern of fear output, and was observed throughout cue presentation. The results reveal an expected vlPAG signal for fear output in an unexpected, cue-inhibited population.

Highlights

The ventrolateral periaqueductal gray is an essential node in a neural circuit for defensive behavior
In the prevailing view of the defensive circuit, threat estimates originate in the amygdala and are relayed to the ventrolateral periaqueductal gray (vlPAG) to organize the behavioral components of fear output, such as freezing (Fanselow, 1994)
A multitude of studies have observed a population of vlPAG single-units showing short-latency excitation to cues predicting foot shock (Tovote et al, 2016; Watson et al, 2016; Ozawa et al, 2017; Groessl et al, 2018)

Summary

Introduction

The ventrolateral periaqueductal gray (vlPAG) is an essential node in a neural circuit for defensive behavior. In the prevailing view of the defensive circuit, threat estimates originate in the amygdala and are relayed to the vlPAG to organize the behavioral components of fear output, such as freezing (Fanselow, 1994). A multitude of studies have observed a population of vlPAG single-units showing short-latency excitation to cues predicting foot shock (Tovote et al, 2016; Watson et al, 2016; Ozawa et al, 2017; Groessl et al, 2018). We recorded vlPAG single-unit activity while rats underwent fear discrimination in which three auditory cues predicted unique foot shock probabilities: danger (p = 1.00), uncertainty (p = 0.375) and safety (p = 0.00) (Wright and McDannald, 2019). Onset single-unit activity reflected the foot shock probability associated with each cue, rather than the level of fear demonstrated to that cue. Short-latency excitatory responses reflect information about threat probability

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