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

  1. Kristina M Wright  Is a corresponding author
  2. Thomas C Jhou
  3. Daniel Pimpinelli
  4. Michael A McDannald  Is a corresponding author
  1. Boston College, United States

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 danger cues - the presumed neural substrate for fear output - signal threat probability in male rats (Wright et al., 2019). Here, we scrutinize the activity of cue-inhibited vlPAG neurons that show decreases in firing to danger cues. 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. Differential firing by this second population 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.

Data availability

Data have been deposited at: http://crcns.org/data-sets/bst/pag-1

The following previously published data sets were used

Article and author information

Author details

  1. Kristina M Wright

    Department of Psychology, Boston College, Chestnut Hill, United States
    For correspondence
    wrightko@bc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1446-3009
  2. Thomas C Jhou

    Department of Psychology, Boston College, Chestnut Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8811-0156
  3. Daniel Pimpinelli

    Department of Psychology, Boston College, Chestnut Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael A McDannald

    Department of Psychology, Boston College, Chestnut Hill, United States
    For correspondence
    michael.mcdannald@bc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8525-1260

Funding

National Institutes of Health (R01MH117791)

  • Michael A McDannald

National Institutes of Health (R00DA034010)

  • Michael A McDannald

National Science Foundation (5106201)

  • Kristina M Wright

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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. The protocol was approved by the Institutional Animal Care and Use Committee of Boston College. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Thorsten Kahnt, Northwestern University Feinberg School of Medicine, United States

Publication history

  1. Received: July 10, 2019
  2. Accepted: September 28, 2019
  3. Accepted Manuscript published: September 30, 2019 (version 1)
  4. Version of Record published: October 30, 2019 (version 2)

Copyright

© 2019, Wright 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

  • 1,036
    Page views
  • 154
    Downloads
  • 11
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Kristina M Wright
  2. Thomas C Jhou
  3. Daniel Pimpinelli
  4. Michael A McDannald
(2019)
Cue-inhibited ventrolateral periaqueductal gray neurons signal fear output and threat probability in male rats
eLife 8:e50054.
https://doi.org/10.7554/eLife.50054

Further reading

    1. Neuroscience
    Lior Matityahu et al.
    Research Article Updated

    Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs. Measurements of this disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feedforward inhibition. Moreover, functional nAChRs are also present on populations of GINs that respond only weakly to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices from mice we show that upon synchronous optogenetic activation of corticostriatal projections blockade of α4β2 nAChRs shortened SPN spike latencies and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond strongly to phasic CIN activation. In particular, the observed decrease in spike latency caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, a parallel hyperpolarization of PV-FSIs, and was occluded by pharmacologically preventing cortical activation of PV-FSIs. Taken together, we describe a role for tonic (as opposed to phasic) activation of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs maintains a GABAergic brake on cortically-driven striatal output by ‘priming’ feedforward inhibition, a process that may shape SPN spike timing, striatal processing, and synaptic plasticity.

    1. Neuroscience
    Sudeshna Das Chakraborty et al.
    Research Article

    Understanding neuronal representations of odor-evoked activities and their progressive transformation from the sensory level to higher brain centers features one of the major aims in olfactory neuroscience. Here, we investigated how odor information is transformed and represented in higher-order neurons of the lateral horn, one of the higher olfactory centers implicated in determining innate behavior, using Drosophila melanogaster. We focused on a subset of third-order glutamatergic lateral horn neurons (LHNs) and characterized their odor coding properties in relation to their presynaptic partner neurons, the projection neurons (PNs) by two-photon functional imaging. We show that odors evoke reproducible, stereotypic, and odor-specific response patterns in LHNs. Notably, odor-evoked responses in these neurons are valence-specific in a way that their response amplitude is positively correlated with innate odor preferences. We postulate that this valence-specific activity is the result of integrating inputs from multiple olfactory channels through second-order neurons. GRASP and micro-lesioning experiments provide evidence that glutamatergic LHNs obtain their major excitatory input from uniglomerular PNs, while they receive an odor-specific inhibition through inhibitory multiglomerular PNs. In summary, our study indicates that odor representations in glutamatergic LHNs encode hedonic valence and odor identity and primarily retain the odor coding properties of second-order neurons.