1. Neuroscience
Download icon

Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage

  1. Jennifer Resnik  Is a corresponding author
  2. Daniel B Polley  Is a corresponding author
  1. Massachusetts Eye and Ear Infirmary, United States
Short Report
  • Cited 24
  • Views 1,871
  • Annotations
Cite this article as: eLife 2017;6:e21452 doi: 10.7554/eLife.21452

Abstract

Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries.

Article and author information

Author details

  1. Jennifer Resnik

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    For correspondence
    Jennifer_Resnik@MEEI.HARVARD.EDU
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0573-0008
  2. Daniel B Polley

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    For correspondence
    Daniel_Polley@meei.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5120-2409

Funding

European Molecular Biology Organization (Long term postdoctoral fellowship)

  • Jennifer Resnik

National Institute on Deafness and Other Communication Disorders (RO1 DC009836)

  • Daniel B Polley

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 Animal Care and Use Committee at the Massachusetts Eye and Ear Infirmary (protocol number 10-03-006) and followed guidelines established by the National Institutes of Health for the care and use of laboratory animals. All surgeries were performed under ketamine and xylazine, and every effort was made to minimize suffering.

Reviewing Editor

  1. Dwight E Bergles, Johns Hopkins School of Medicine, United States

Publication history

  1. Received: September 13, 2016
  2. Accepted: March 20, 2017
  3. Accepted Manuscript published: March 21, 2017 (version 1)
  4. Version of Record published: April 3, 2017 (version 2)

Copyright

© 2017, Resnik & Polley

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

  • 1,871
    Page views
  • 437
    Downloads
  • 24
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, 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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Joshua B Burt et al.
    Research Advance

    Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor (Preller et al., 2018). Here, we integrate brain-wide transcriptomics with biophysically based circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical blood oxygen level-dependent (BOLD) functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.

    1. Neuroscience
    Chin-Hsuan Chia et al.
    Short Report

    Sleep is essential in maintaining physiological homeostasis in the brain. While the underlying mechanism is not fully understood, a 'synaptic homeostasis' theory has been proposed that synapses continue to strengthen during awake, and undergo downscaling during sleep. This theory predicts that brain excitability increases with sleepiness. Here, we collected transcranial magnetic stimulation (TMS) measurements in 38 subjects in a 34-hour program, and decoded the relationship between cortical excitability and self-report sleepiness using advanced statistical methods. By utilizing a combination of partial least squares (PLS) regression and mixed-effect models, we identified a robust pattern of excitability changes, which can quantitatively predict the degree of sleepiness. Moreover, we found that synaptic strengthen occurred in both excitatory and inhibitory connections after sleep deprivation. In sum, our study provides supportive evidence for the synaptic homeostasis theory in human sleep and clarifies the process of synaptic strength modulation during sleepiness.