Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning

Abstract

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.

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 all Figures

Article and author information

Author details

  1. Haneen Kayyal

    Sagol Department of Neurobiology, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4429-3514
  2. Sailendrakumar Kolatt Chandran

    Sagol Department of Neurobiology, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9805-8096
  3. Adonis Yiannakas

    Sagol Department of Neurobiology, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Nathaniel Gould

    Sagol Department of Neurobiology, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Mohammad Khamaisy

    Sagol Department of Neurobiology, University of Haifa, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Kobi Rosenblum

    Sagol Department of Neurobiology, University of Haifa, Haifa, Israel
    For correspondence
    kobir@psy.haifa.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4827-0336

Funding

Israel Science Foundation (isf 946/17)

  • Kobi Rosenblum

Israel Science Foundation (isf 258/20)

  • Kobi Rosenblum

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 experiments and procedures conducted were approved by the University of Haifa Animal Care and Use committee under Ethical license 554/18 and were in accordance with the National Institutes of Health guidelines for ethical treatment of animals.

Reviewing Editor

  1. Mathieu Wolff, CNRS, University of Bordeaux, France

Version history

  1. Received: January 19, 2021
  2. Accepted: June 29, 2021
  3. Accepted Manuscript published: July 5, 2021 (version 1)
  4. Version of Record published: July 15, 2021 (version 2)

Copyright

© 2021, Kayyal 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

  • 1,855
    Page views
  • 258
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, 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. Haneen Kayyal
  2. Sailendrakumar Kolatt Chandran
  3. Adonis Yiannakas
  4. Nathaniel Gould
  5. Mohammad Khamaisy
  6. Kobi Rosenblum
(2021)
Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning
eLife 10:e66686.
https://doi.org/10.7554/eLife.66686

Further reading

    1. Neuroscience
    Jing Wang, Hamid Azimi ... Gregor Rainer
    Research Article

    The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFP) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz, and uncovered a striking phase locking between the V1 local field potential (LFP) and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

    1. Neuroscience
    Anna C Geuzebroek, Hannah Craddock ... Simon P Kelly
    Research Article Updated

    Decisions about noisy stimuli are widely understood to be made by accumulating evidence up to a decision bound that can be adjusted according to task demands. However, relatively little is known about how such mechanisms operate in continuous monitoring contexts requiring intermittent target detection. Here, we examined neural decision processes underlying detection of 1 s coherence targets within continuous random dot motion, and how they are adjusted across contexts with weak, strong, or randomly mixed weak/strong targets. Our prediction was that decision bounds would be set lower when weak targets are more prevalent. Behavioural hit and false alarm rate patterns were consistent with this, and were well captured by a bound-adjustable leaky accumulator model. However, beta-band EEG signatures of motor preparation contradicted this, instead indicating lower bounds in the strong-target context. We thus tested two alternative models in which decision-bound dynamics were constrained directly by beta measurements, respectively, featuring leaky accumulation with adjustable leak, and non-leaky accumulation of evidence referenced to an adjustable sensory-level criterion. We found that the latter model best explained both behaviour and neural dynamics, highlighting novel means of decision policy regulation and the value of neurally informed modelling.