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.
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.
Data from: Ventrolateral periaqueductal gray neurons prioritize threat probability over fear outputCRCNS, doi:10.6080/K0R49P0V.
- Michael A McDannald
- 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.
- Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States
© 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.
Genuinely new discovery transcends existing knowledge. Despite this, many analyses in systems neuroscience neglect to test new speculative hypotheses against benchmark empirical facts. Some of these analyses inadvertently use circular reasoning to present existing knowledge as new discovery. Here, I discuss that this problem can confound key results and estimate that it has affected more than three thousand studies in network neuroscience over the last decade. I suggest that future studies can reduce this problem by limiting the use of speculative evidence, integrating existing knowledge into benchmark models, and rigorously testing proposed discoveries against these models. I conclude with a summary of practical challenges and recommendations.
The synchronization of canonical fast sleep spindle activity (12.5–16 Hz, adult-like) precisely during the slow oscillation (0.5–1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5–6, 8–11, and 14–18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups—but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.