On cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

  1. Robson Scheffer-Teixeira
  2. Adriano BL Tort  Is a corresponding author
  1. Federal University of Rio Grande do Norte, Brazil

Abstract

Phase-amplitude coupling between theta and multiple gamma sub-bands is a hallmark of hippocampal activity and believed to take part in information routing. More recently, theta and gamma oscillations were also reported to exhibit phase-phase coupling, or n:m phase-locking, suggesting an important mechanism of neuronal coding that has long received theoretical support. However, by analyzing simulated and actual LFPs, here we question the existence of theta-gamma phase-phase coupling in the rat hippocampus. We show that the quasi-linear phase shifts introduced by filtering lead to spurious coupling levels in both white noise and hippocampal LFPs, which highly depend on epoch length, and that significant coupling may be falsely detected when employing improper surrogate methods. We also show that waveform asymmetry and frequency harmonics may generate artifactual n:m phase-locking. Studies investigating phase-phase coupling should rely on appropriate statistical controls and be aware of confounding factors; otherwise, they could easily fall into analysis pitfalls.

Data availability

The following data sets were generated
    1. Scheffer-Teixeira R
    2. Tort A.
    (2016) Multisite LFP recordings from the rat hippocampus during REM sleep
    Available at Dryad Digital Repository under a CC0 Public Domain Dedication.
The following previously published data sets were used

Article and author information

Author details

  1. Robson Scheffer-Teixeira

    Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  2. Adriano BL Tort

    Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil
    For correspondence
    tort@neuro.ufrn.br
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9877-7816

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico

  • Robson Scheffer-Teixeira
  • Adriano BL Tort

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

  • Robson Scheffer-Teixeira
  • Adriano BL Tort

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 our local institutional ethics committee (Comissão de Ética no Uso de Animais - CEUA/UFRN, protocol number 060/2011) and were in accordance with the National Institutes of Health guidelines.

Reviewing Editor

  1. Frances K Skinner, University Health Network, Canada

Publication history

  1. Received: August 10, 2016
  2. Accepted: December 5, 2016
  3. Accepted Manuscript published: December 7, 2016 (version 1)
  4. Version of Record published: December 29, 2016 (version 2)

Copyright

© 2016, Scheffer-Teixeira & Tort

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.

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  1. Robson Scheffer-Teixeira
  2. Adriano BL Tort
(2016)
On cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus
eLife 5:e20515.
https://doi.org/10.7554/eLife.20515
  1. Further reading

Further reading

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    Research Article Updated

    Defining the origin of neuronal diversity is a major challenge in developmental neurobiology. The Drosophila visual system is an excellent paradigm to study how cellular diversity is generated. Photoreceptors from the eye disc grow their axons into the optic lobe and secrete Hedgehog (Hh) to induce the lamina, such that for every unit eye there is a corresponding lamina unit made up of post-mitotic precursors stacked into columns. Each differentiated column contains five lamina neuron types (L1-L5), making it the simplest neuropil in the optic lobe, yet how this diversity is generated was unknown. Here, we found that Hh pathway activity is graded along the distal-proximal axis of lamina columns, and further determined that this gradient in pathway activity arises from a gradient of Hh ligand. We manipulated Hh pathway activity cell autonomously in lamina precursors and non-cell autonomously by inactivating the Hh ligand and by knocking it down in photoreceptors. These manipulations showed that different thresholds of activity specify unique cell identities, with more proximal cell types specified in response to progressively lower Hh levels. Thus, our data establish that Hh acts as a morphogen to pattern the lamina. Although this is the first such report during Drosophila nervous system development, our work uncovers a remarkable similarity with the vertebrate neural tube, which is patterned by Sonic Hh. Altogether, we show that differentiating neurons can regulate the neuronal diversity of their distant target fields through morphogen gradients.

    1. Developmental Biology
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    Anadika R Prasad, Inês Lago-Baldaia ... Vilaiwan M Fernandes
    Research Article Updated

    Neural circuit formation and function require that diverse neurons are specified in appropriate numbers. Known strategies for controlling neuronal numbers involve regulating either cell proliferation or survival. We used the Drosophila visual system to probe how neuronal numbers are set. Photoreceptors from the eye-disc induce their target field, the lamina, such that for every unit eye there is a corresponding lamina unit (column). Although each column initially contains ~6 post-mitotic lamina precursors, only 5 differentiate into neurons, called L1-L5; the ‘extra’ precursor, which is invariantly positioned above the L5 neuron in each column, undergoes apoptosis. Here, we showed that a glial population called the outer chiasm giant glia (xgO), which resides below the lamina, secretes multiple ligands to induce L5 differentiation in response to epidermal growth factor (EGF) from photoreceptors. By forcing neuronal differentiation in the lamina, we uncovered that though fated to die, the ‘extra’ precursor is specified as an L5. Therefore, two precursors are specified as L5s but only one differentiates during normal development. We found that the row of precursors nearest to xgO differentiate into L5s and, in turn, antagonise differentiation signalling to prevent the ‘extra’ precursors from differentiating, resulting in their death. Thus, an intricate interplay of glial signals and feedback from differentiating neurons defines an invariant and stereotyped pattern of neuronal differentiation and programmed cell death to ensure that lamina columns each contain exactly one L5 neuron.