Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex

  1. Sebastian H Bitzenhofer  Is a corresponding author
  2. Elena A Westeinde
  3. Han-Xiong Bear Zhang
  4. Jeffry S Isaacson  Is a corresponding author
  1. University of California, San Diego, United States

Abstract

Olfactory information is encoded in lateral entorhinal cortex (LEC) by two classes of layer 2 (L2) principal neurons: fan and pyramidal cells. However, the functional properties of L2 cells and how they contribute to odor coding are unclear. Here, we show in awake mice that L2 cells respond to odors early during single sniffs and that LEC is essential for rapid discrimination of both odor identity and intensity. Population analyses of L2 ensembles reveals that rate coding distinguishes odor identity, but firing rates are only weakly concentration-dependent and changes in spike timing can represent odor intensity. L2 principal cells differ in afferent olfactory input and connectivity with inhibitory circuits and the relative timing of pyramidal and fan cell spikes provides a temporal code for odor intensity. Downstream, intensity is encoded purely by spike timing in hippocampal CA1. Together, these results reveal the unique processing of odor information by LEC subcircuits and highlight the importance of temporal coding in higher olfactory areas.

Data availability

Source data is provided for each figure containing the numerical data used to generate the figures.

Article and author information

Author details

  1. Sebastian H Bitzenhofer

    Department of Neurosciences, University of California, San Diego, La Jolla, United States
    For correspondence
    seb.bitzenhofer@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
  2. Elena A Westeinde

    Department of Neurosciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Han-Xiong Bear Zhang

    Department of Neurosciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jeffry S Isaacson

    Department of Neurosciences, University of California, San Diego, La Jolla, United States
    For correspondence
    jisaacson@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9052-5211

Funding

National Institute on Deafness and Other Communication Disorders (R01DC04682)

  • Jeffry S Isaacson

National Institute on Deafness and Other Communication Disorders (R01DC015239)

  • Jeffry S Isaacson

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

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

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 (#S977M)) of the UCSD. All surgery was performed under halothane anesthesia, and every effort was made to minimize suffering.

Version history

  1. Preprint posted: August 19, 2021 (view preprint)
  2. Received: October 28, 2021
  3. Accepted: February 4, 2022
  4. Accepted Manuscript published: February 7, 2022 (version 1)
  5. Version of Record published: February 21, 2022 (version 2)

Copyright

© 2022, Bitzenhofer 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

  • 1,995
    views
  • 312
    downloads
  • 20
    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. Sebastian H Bitzenhofer
  2. Elena A Westeinde
  3. Han-Xiong Bear Zhang
  4. Jeffry S Isaacson
(2022)
Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex
eLife 11:e75065.
https://doi.org/10.7554/eLife.75065

Share this article

https://doi.org/10.7554/eLife.75065

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Kenneth Chiou, Noah Snyder-Mackler
    Insight

    Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.

    1. Neuroscience
    Flavio J Schmidig, Simon Ruch, Katharina Henke
    Research Article

    We are unresponsive during slow-wave sleep but continue monitoring external events for survival. Our brain wakens us when danger is imminent. If events are non-threatening, our brain might store them for later consideration to improve decision-making. To test this hypothesis, we examined whether novel vocabulary consisting of simultaneously played pseudowords and translation words are encoded/stored during sleep, and which neural-electrical events facilitate encoding/storage. An algorithm for brain-state-dependent stimulation selectively targeted word pairs to slow-wave peaks or troughs. Retrieval tests were given 12 and 36 hr later. These tests required decisions regarding the semantic category of previously sleep-played pseudowords. The sleep-played vocabulary influenced awake decision-making 36 hr later, if targeted to troughs. The words’ linguistic processing raised neural complexity. The words’ semantic-associative encoding was supported by increased theta power during the ensuing peak. Fast-spindle power ramped up during a second peak likely aiding consolidation. Hence, new vocabulary played during slow-wave sleep was stored and influenced decision-making days later.