Medial entorhinal cortex activates in a traveling wave in the rat

  1. Jesus J Hernández-Pérez  Is a corresponding author
  2. Keiland W Cooper
  3. Ehren L Newman
  1. Indiana University Bloomington, United States

Abstract

Traveling waves are hypothesized to support the long-range coordination of anatomically distributed circuits. Whether separate strongly-interacting circuits exhibit traveling waves remains unknown. The hippocampus exhibits traveling 'theta' waves and interacts strongly with the medial entorhinal cortex (MEC). To determine whether the MEC also activates in a traveling wave, we performed extracellular recordings of LFP and multi-unit activity along the MEC. These recordings revealed progressive phase shifts in activity, indicating that the MEC also activates in a traveling wave. Variation in theta waveform along the region, generated by gradients in local physiology, contributed to the observed phase shifts. Removing waveform-related phase shifts left significant residual phase shifts. The residual phase shifts covaried with theta frequency in a manner consistent with those generated by weakly coupled oscillators. These results show that coordination of anatomically distributed circuits could be enabled by traveling waves but reveal heterogeneity in the mechanisms generating those waves.

Data availability

Data files have bee be uploaded to crcns.org http://dx.doi.org/10.6080/K0C53J2R

The following data sets were generated

Article and author information

Author details

  1. Jesus J Hernández-Pérez

    Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, United States
    For correspondence
    jjhern@iu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6963-4712
  2. Keiland W Cooper

    Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0358-9645
  3. Ehren L Newman

    Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

Whitehall Foundation

  • Ehren L Newman

Consejo Nacional de Ciencia y Tecnología (232364)

  • Jesus J Hernández-Pérez

Indiana University Bloomington

  • Ehren L Newman

The funders provided resources for the study design, data collection, and interpretation.

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 (#18-026) of Indiana University, Bloomington. The protocol was approved by the Committee on the Ethics of Animal Experiments of Indiana University, Bloomington (Animal Welfare Assurance Number D16-00587). All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Copyright

© 2020, Hernández-Pérez 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

  • 2,543
    views
  • 401
    downloads
  • 16
    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. Jesus J Hernández-Pérez
  2. Keiland W Cooper
  3. Ehren L Newman
(2020)
Medial entorhinal cortex activates in a traveling wave in the rat
eLife 9:e52289.
https://doi.org/10.7554/eLife.52289

Share this article

https://doi.org/10.7554/eLife.52289

Further reading

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.