1. Neuroscience

Spectral signature and behavioral consequence of spontaneous shifts of pupil-linked arousal in human

  1. Ella Podvalny
  2. Leana E King
  3. Biyu J He  Is a corresponding author
  1. New York University School of Medicine, United States
https://doi.org/10.7554/eLife.68265
Share this article
Cite this article
  1. Ella Podvalny
  2. Leana E King
  3. Biyu J He
(2021)
Spectral signature and behavioral consequence of spontaneous shifts of pupil-linked arousal in human
eLife 10:e68265.
https://doi.org/10.7554/eLife.68265
  2. Download BibTeX
  3. Download .RIS

Abstract

Arousal levels perpetually rise and fall spontaneously. How markers of arousal - pupil size and frequency content of brain activity - relate to each other and influence behavior in humans is poorly understood. We simultaneously monitored magnetoencephalography and pupil in healthy volunteers at rest and during a visual perceptual decision-making task. Spontaneously varying pupil size correlates with power of brain activity in most frequency bands across large-scale resting-state cortical networks. Pupil size recorded at prestimulus baseline correlates with subsequent shifts in detection bias (c) and sensitivity (d'). When dissociated from pupil-linked state, prestimulus spectral power of resting state networks still predicts perceptual behavior. Fast spontaneous pupil constriction and dilation correlate with large-scale brain activity as well but not perceptual behavior. Our results illuminate the relation between central and peripheral arousal markers and their respective roles in human perceptual decision-making.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data are available as csv files for all figures except for whole brain images.

Article and author information

Author details

  1. Ella Podvalny

    Neurobiology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Leana E King

    Neuroscience Institute, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Biyu J He

    Neuroscience Institute, New York University School of Medicine, New York, United States
    For correspondence
    biyu.jade.he@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1549-1351

Funding

National Science Foundation (BCS- 1753218)

  • Biyu J He

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

Ethics

Human subjects: All participants provided written informed consent. The experiment was approved by the Institutional Review Board of the National Institute of Neurological Disorders and Stroke (protocol #14-N-0002).

Copyright

© 2021, Podvalny 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

  • 2,588
    views
  • 423
    downloads
  • 49
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

Share this article

https://doi.org/10.7554/eLife.68265

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Rab10 regulates neuropeptide release by maintaining Ca2+ homeostasis and protein synthesis

    Jian Dong, Mian Chen ... Matthijs Verhage
    Research Article

    Dense core vesicles (DCVs) transport and release various neuropeptides and neurotrophins that control diverse brain functions, but the DCV secretory pathway remains poorly understood. Here, we tested a prediction emerging from invertebrate studies about the crucial role of the intracellular trafficking GTPase Rab10, by assessing DCV exocytosis at single-cell resolution upon acute Rab10 depletion in mature mouse hippocampal neurons, to circumvent potential confounding effects of Rab10’s established role in neurite outgrowth. We observed a significant inhibition of DCV exocytosis in Rab10-depleted neurons, whereas synaptic vesicle exocytosis was unaffected. However, rather than a direct involvement in DCV trafficking, this effect was attributed to two ER-dependent processes, ER-regulated intracellular Ca2+ dynamics, and protein synthesis. Gene Ontology analysis of differentially expressed proteins upon Rab10 depletion identified substantial alterations in synaptic and ER/ribosomal proteins, including the Ca2+ pump SERCA2. In addition, ER morphology and dynamics were altered, ER Ca2+ levels were depleted, and Ca2+ homeostasis was impaired in Rab10-depleted neurons. However, Ca2+ entry using a Ca2+ ionophore still triggered less DCV exocytosis. Instead, leucine supplementation, which enhances protein synthesis, largely rescued DCV exocytosis deficiency. We conclude that Rab10 is required for neuropeptide release by maintaining Ca2+ dynamics and regulating protein synthesis. Furthermore, DCV exocytosis appeared more dependent on (acute) protein synthesis than synaptic vesicle exocytosis.

    1. Neuroscience

    Neuronal Signaling: At the crossroads of calcium signaling, protein synthesis and neuropeptide release

    Jakob Rupert, Dragomir Milovanovic
    Insight

    By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.

    1. Neuroscience

    Peripheral opioid receptor antagonism alleviates fentanyl-induced cardiorespiratory depression and is devoid of aversive behavior

    Brian C Ruyle, Sarah Masud ... Jose A Morón
    Research Article

    Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.