Online integration of sensory and emotional (fear) memories in the rat medial temporal lobe

  1. Francesca S Wong
  2. R Fred Westbrook
  3. Nathan M Holmes  Is a corresponding author
  1. University of New South Wales, Australia

Abstract

How does a stimulus never associated with danger become frightening? The present study addressed this question using a sensory preconditioning task with rats. In this task, rats integrate a sound-light memory formed in stage 1 with a light-danger memory formed in stage 2, as they show fear when tested with the sound in stage 3. Here we show that this integration occurs 'online' during stage 2: when activity in the region that consolidated the sound-light memory (perirhinal cortex) was inhibited during formation of the light-danger memory, rats no longer showed fear when tested with the sound but continued to fear the light. Thus, fear that accrues to a stimulus paired with danger simultaneously spreads to its past associates, thereby roping those associates into a fear memory network.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 4 and 5.

Article and author information

Author details

  1. Francesca S Wong

    School of Psychology, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. R Fred Westbrook

    School of Psychology, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Nathan M Holmes

    School of Psychology, University of New South Wales, Sydney, Australia
    For correspondence
    n.holmes@unsw.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0592-2026

Funding

Australian Research Council (DP170103952)

  • Nathan M Holmes

National Health and Medical Research Council (APP1146999)

  • Nathan M Holmes

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 guidelines published by the National Health and Medical Research Council in Australia. All of the animals were handled according to approved Animal Care and Ethics Committee (ACEC) protocols at the University of New South Wales (Permit Number: ACEC 17/139A). All surgery was performed under ketamine-xylazine induced anesthesia, and every effort was made to minimize suffering.

Copyright

© 2019, Wong 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

  • 1,863
    views
  • 288
    downloads
  • 41
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Francesca S Wong
  2. R Fred Westbrook
  3. Nathan M Holmes
(2019)
Online integration of sensory and emotional (fear) memories in the rat medial temporal lobe
eLife 8:e47085.
https://doi.org/10.7554/eLife.47085

Share this article

https://doi.org/10.7554/eLife.47085

Further reading

    1. Neuroscience
    Eleni Hackwell, Sharon R Ladyman ... David R Grattan
    Research Article

    The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.

    1. Neuroscience
    Nico A Flierman, Sue Ann Koay ... Chris I De Zeeuw
    Research Article

    The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay. We found that single-unit DN neurons modulated spiking activity over the entire time course of the task, and that their activity often bridged temporally separated intra-trial events, yet in a heterogeneous manner. To better understand the heterogeneous relationship between task structure, behavioral performance, and neural dynamics, we constructed a behavioral, an encoding, and a decoding model. Both NHPs showed different behavioral strategies, which influenced the performance. Activity of the DN neurons reflected the unique strategies, with the direction of the visual stimulus frequently being encoded long before an upcoming saccade. Moreover, the latency of the ramping activity of DN neurons following presentation of the visual stimulus was shorter in the better performing NHP. Labeling with the retrograde tracer Cholera Toxin B in the recording location in the DN indicated that these neurons predominantly receive inputs from Purkinje cells in the D1 and D2 zones of the lateral cerebellum as well as neurons of the principal olive and medial pons, all regions known to connect with neurons in the prefrontal cortex contributing to planning of saccades. Together, our results highlight that DN neurons can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components.