Dorsal Periaqueductal gray ensembles represent approach and avoidance states
Abstract
Animals must balance needs to approach threats for risk-assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threat-avoidance ensemble in mice that showed higher activity far from threats such as the open arms of the elevated plus maze and a live predator. These cells were also more active during threat-avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat-approach ensemble was more active during risk-assessment behaviors and near threats. Furthermore, unsupervised methods showed that avoidance/approach states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat-avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk-assessment and danger avoidance.
Data availability
All data was uploaded to dryad and all code was uploaded to github.https://datadryad.org/stash/share/4GezSjw4dvDJClAWa_zRoNWioH9qzGtDCJjLQ89HVoAhttps://doi.org/10.5068/D1TM2Ghttps://github.com/schuettepeter/eLife_dPAG-ensembles-represent-approach-and-avoidance-states
-
Data from: Dorsal Periaqueductal gray ensembles represent approach and avoidance statesDryad Digital Repository, 10.5068/D1TM2G.
Article and author information
Author details
Funding
National Institutes of Health (R00 MH106649)
- Avishek Adhikari
National Institutes of Health (F31 MH121050-01A1)
- Mimi Q La-Vu
Achievement Rewards for College Scientists Foundation
- Mimi Q La-Vu
National Institutes of Health (R01 MH119089)
- Avishek Adhikari
Brain and Behavior Research Foundation (22663)
- Avishek Adhikari
Brain and Behavior Research Foundation (27654)
- Fernando MCV Reis
National Science Foundation (DGE-1650604)
- Peter J Schuette
Fundação de Amparo à Pesquisa do Estado de São Paulo (2015/23092-3)
- Fernando MCV Reis
Fundação de Amparo à Pesquisa do Estado de São Paulo (2017/08668-1)
- Fernando MCV Reis
Fundação de Amparo à Pesquisa do Estado de São Paulo (2014/05432-9)
- Newton S Canteras
Hellman Foundation
- Avishek Adhikari
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures have been approved by the University of California, Los Angeles Institutional Animal Care and Use Committee, protocols 2017-011 and 2017-075.
Reviewing Editor
- Mihaela D Iordanova, Concordia University, Canada
Version history
- Received: November 16, 2020
- Accepted: May 5, 2021
- Accepted Manuscript published: May 6, 2021 (version 1)
- Version of Record published: May 19, 2021 (version 2)
Copyright
© 2021, Reis et al.
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.
Metrics
-
- 2,741
- Page views
-
- 390
- Downloads
-
- 12
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
- Structural Biology and Molecular Biophysics
Acid-sensing ion channels (ASICs) are trimeric proton-gated sodium channels. Recent work has shown that these channels play a role in necroptosis following prolonged acidic exposure like occurs in stroke. The C-terminus of ASIC1a is thought to mediate necroptotic cell death through interaction with receptor interacting serine threonine kinase 1 (RIPK1). This interaction is hypothesized to be inhibited at rest via an interaction between the C- and N-termini which blocks the RIPK1 binding site. Here, we use two transition metal ion FRET methods to investigate the conformational dynamics of the termini at neutral and acidic pH. We do not find evidence that the termini are close enough to be bound while the channel is at rest and find that the termini may modestly move closer together during acidification. At rest, the N-terminus adopts a conformation parallel to the membrane about 10 Å away. The distal end of the C-terminus may also spend time close to the membrane at rest. After acidification, the proximal portion of the N-terminus moves marginally closer to the membrane whereas the distal portion of the C-terminus swings away from the membrane. Together these data suggest that a new hypothesis for RIPK1 binding during stroke is needed.
-
- Neuroscience
Decisions under uncertainty are often biased by the history of preceding sensory input, behavioral choices, or received outcomes. Behavioral studies of perceptual decisions suggest that such history-dependent biases affect the accumulation of evidence and can be adapted to the correlation structure of the sensory environment. Here, we systematically varied this correlation structure while human participants performed a canonical perceptual choice task. We tracked the trial-by-trial variations of history biases via behavioral modeling and of a neural signature of decision formation via magnetoencephalography (MEG). The history bias was flexibly adapted to the environment and exerted a selective effect on the build-up (not baseline level) of action-selective motor cortical activity during decision formation. This effect added to the impact of the current stimulus. We conclude that the build-up of action plans in human motor cortical circuits is shaped by dynamic prior expectations that result from an adaptive interaction with the environment.