Cognitive experience alters cortical involvement in goal-directed navigation

Abstract

Neural activity in the mammalian cortex has been studied extensively during decision tasks, and recent work aims to identify under what conditions cortex is actually necessary for these tasks. We discovered that mice with distinct cognitive experiences, beyond sensory and motor learning, use different cortical areas and neural activity patterns to solve the same navigation decision task, revealing past learning as a critical determinant of whether cortex is necessary for goal-directed navigation. We used optogenetics and calcium imaging to study the necessity and neural activity of multiple cortical areas in mice with different training histories. Posterior parietal cortex and retrosplenial cortex were mostly dispensable for accurate performance of a simple navigation task. In contrast, these areas were essential for the same simple task when mice were previously trained on complex tasks with delay periods or association switches. Multi-area calcium imaging showed that, in mice with complex-task experience, single-neuron activity had higher selectivity and neuron-neuron correlations were weaker, leading to codes with higher task information. Therefore, past experience is a key factor in determining whether cortical areas have a causal role in goal-directed navigation.

Data availability

Data have been deposited in Dryad with the DOI: https://doi.org/10.5061/dryad.34tmpg4nr.

The following data sets were generated

Article and author information

Author details

  1. Charlotte Arlt

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Roberto Barroso-Luque

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Shinichiro Kira

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Carissa A Bruno

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7126-2185
  5. Ningjing Xia

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Selmaan N Chettih

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sofia Soares

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Noah L Pettit

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Christopher D Harvey

    Department of Neurobiology, Harvard Medical School, Boston, United States
    For correspondence
    harvey@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9850-2268

Funding

National Institutes of Health (R01 MH107620)

  • Christopher D Harvey

JSPS Overseas Research Fellowship

  • Shinichiro Kira

EMBO Postdoctoral Fellowship

  • Sofia Soares

Stuart H.Q. & Victoria Quan Fellowship

  • Noah L Pettit

National Institutes of Health (R01 NS089521)

  • Christopher D Harvey

National Institutes of Health (R01 NS108410)

  • Christopher D Harvey

National Institutes of Health (DP1 MH125776)

  • Christopher D Harvey

Louis Perry Jones Postdoctoral Fellowship

  • Charlotte Arlt

Alice and Joseph Brooks Postdoctoral Fellowship

  • Charlotte Arlt

Uehara Foundation Research Fellowship

  • Shinichiro Kira

Leonard and Isabelle Goldenson Postdoctoral Fellowship

  • Shinichiro Kira

NARSAD Young Investigator Grant

  • Shinichiro Kira

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 experimental procedures were approved by the Harvard Medical School Institutional Animal Care and Use Committee (protocol # 00000073-6) and were performed in compliance with the Guide for the Care and Use of Laboratory Animals.

Reviewing Editor

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

Publication history

  1. Received: December 2, 2021
  2. Accepted: June 22, 2022
  3. Accepted Manuscript published: June 23, 2022 (version 1)

Copyright

© 2022, Arlt 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

  • 328
    Page views
  • 147
    Downloads
  • 0
    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. Charlotte Arlt
  2. Roberto Barroso-Luque
  3. Shinichiro Kira
  4. Carissa A Bruno
  5. Ningjing Xia
  6. Selmaan N Chettih
  7. Sofia Soares
  8. Noah L Pettit
  9. Christopher D Harvey
(2022)
Cognitive experience alters cortical involvement in goal-directed navigation
eLife 11:e76051.
https://doi.org/10.7554/eLife.76051

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Xin-Yao Sun et al.
    Research Article Updated

    Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood–brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Bilal Cakir, In-Hyun Park
    Insight

    Fusing brain organoids with blood vessel organoids leads to the incorporation of non-neural endothelial cells and microglia into the brain organoids.