Multiple time-scales of decision making in the hippocampus and prefrontal cortex

  1. Wenbo Tang
  2. Justin D Shin
  3. Shantanu P Jadhav  Is a corresponding author
  1. Brandeis University, United States

Abstract

The prefrontal cortex and hippocampus are crucial for memory-guided decision-making. Neural activity in the hippocampus exhibits place-cell sequences at multiple timescales, including slow behavioral sequences (~seconds) and fast theta sequences (~100-200 ms) within theta oscillation cycles. How prefrontal ensembles interact with hippocampal sequences to support decision-making is unclear. Here, we examined simultaneous hippocampal and prefrontal ensemble activity in rats during learning of a spatial working-memory decision task. We found clear theta sequences in prefrontal cortex, nested within its behavioral sequences. In both regions, behavioral sequences maintained representations of current choices during navigation. In contrast, hippocampal theta sequences encoded alternatives for deliberation, and were coordinated with prefrontal theta sequences that predicted upcoming choices. During error trials, these representations were preserved to guide ongoing behavior, whereas replay sequences during inter-trial periods were impaired prior to navigation. These results establish cooperative interaction between hippocampal and prefrontal sequences at multiple timescales for memory-guided decision-making.

Data availability

All data generated or analysed during this study are included in the manuscript and source data files.

Article and author information

Author details

  1. Wenbo Tang

    Neuroscience, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Justin D Shin

    Neuroscience, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Shantanu P Jadhav

    Neuroscience & Psychology, Brandeis University, Waltham, United States
    For correspondence
    shantanu@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5821-0551

Funding

National Institutes of Health (R01 MH112661)

  • Shantanu P Jadhav

Richard and Susan Smith Family Foundation (Odyssey award)

  • Shantanu P Jadhav

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 were approved by the Institutional Animal Care and Use Committee at Brandeis University (protocol # 21001) and conformed to US National Institutes of Health guidelines.

Reviewing Editor

  1. Laura L. Colgin

Version history

  1. Received: January 4, 2021
  2. Accepted: March 5, 2021
  3. Accepted Manuscript published: March 8, 2021 (version 1)
  4. Version of Record published: March 25, 2021 (version 2)

Copyright

© 2021, Tang 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

  • 6,239
    Page views
  • 842
    Downloads
  • 36
    Citations

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

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. Wenbo Tang
  2. Justin D Shin
  3. Shantanu P Jadhav
(2021)
Multiple time-scales of decision making in the hippocampus and prefrontal cortex
eLife 10:e66227.
https://doi.org/10.7554/eLife.66227

Share this article

https://doi.org/10.7554/eLife.66227

Further reading

    1. Developmental Biology
    2. Neuroscience
    Athina Keramidioti, Sandra Schneid ... Charles N David
    Research Article

    The Hydra nervous system is the paradigm of a ‘simple nerve net’. Nerve cells in Hydra, as in many cnidarian polyps, are organized in a nerve net extending throughout the body column. This nerve net is required for control of spontaneous behavior: elimination of nerve cells leads to polyps that do not move and are incapable of capturing and ingesting prey (Campbell, 1976). We have re-examined the structure of the Hydra nerve net by immunostaining fixed polyps with a novel antibody that stains all nerve cells in Hydra. Confocal imaging shows that there are two distinct nerve nets, one in the ectoderm and one in the endoderm, with the unexpected absence of nerve cells in the endoderm of the tentacles. The nerve nets in the ectoderm and endoderm do not contact each other. High-resolution TEM (transmission electron microscopy) and serial block face SEM (scanning electron microscopy) show that the nerve nets consist of bundles of parallel overlapping neurites. Results from transgenic lines show that neurite bundles include different neural circuits and hence that neurites in bundles require circuit-specific recognition. Nerve cell-specific innexins indicate that gap junctions can provide this specificity. The occurrence of bundles of neurites supports a model for continuous growth and differentiation of the nerve net by lateral addition of new nerve cells to the existing net. This model was confirmed by tracking newly differentiated nerve cells.

    1. Neuroscience
    Anna-Maria Grob, Hendrik Heinbockel ... Lars Schwabe
    Research Article

    Maintaining an accurate model of the world relies on our ability to update memory representations in light of new information. Previous research on the integration of new information into memory mainly focused on the hippocampus. Here, we hypothesized that the angular gyrus, known to be involved in episodic memory and imagination, plays a pivotal role in the insight-driven reconfiguration of memory representations. To test this hypothesis, participants received continuous theta burst stimulation (cTBS) over the left angular gyrus or sham stimulation before gaining insight into the relationship between previously separate life-like animated events in a narrative-insight task. During this task, participants also underwent EEG recording and their memory for linked and non-linked events was assessed shortly thereafter. Our results show that cTBS to the angular gyrus decreased memory for the linking events and reduced the memory advantage for linked relative to non-linked events. At the neural level, cTBS targeting the angular gyrus reduced centro-temporal coupling with frontal regions and abolished insight-induced neural representational changes for events linked via imagination, indicating impaired memory reconfiguration. Further, the cTBS group showed representational changes for non-linked events that resembled the patterns observed in the sham group for the linked events, suggesting failed pruning of the narrative in memory. Together, our findings demonstrate a causal role of the left angular gyrus in insight-related memory reconfigurations.