Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
This Week in The Journal

This Week in The Journal

Teresa Esch [Ph.D.]
Journal of Neuroscience 23 February 2022, 42 (8) 1374; DOI: https://doi.org/10.1523/JNEUROSCI.twij.42.8.2022
Teresa Esch
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Distorted Tonotopy after Noise-Induced Hearing Loss

Satyabrata Parida and Michael G. Heinz

(see pages 1477–1490)

Sounds entering the ear vibrate the cochlear basilar membrane, activating inner hair cells, which excite auditory nerve fibers. Different sound frequencies (pitches) cause maximal vibration at different locations along the basilar membrane, producing a tonotopic map in which auditory nerves innervating different locations respond most strongly to a particular sound frequency, called their characteristic frequency. Importantly, natural sounds comprise multiple frequencies, and thus vibrate multiple points along the basilar membrane.

Outer hair cells amplify local vibration of the basilar membrane, increasing sensitivity to quiet sounds, while dampening nearby vibrations and sharpening frequency tuning of auditory fibers. Exposure to loud noise or certain toxins damages outer hair cells, increasing auditory thresholds, broadening tuning curves, and altering cross-frequency interactions. Hearing aids can compensate for increased thresholds but not for changes in tuning, and hearing-aid wearers typically continue to have difficulty understanding speech in noisy environments (Lesica, 2018, Trends Neurosci 41:174). This indicates that speech comprehension in noise relies on factors other than auditory threshold. Remarkably, however, few studies examining how hearing loss affects sound encoding have used natural speech in noise as the auditory stimulus. By using such stimuli, Parida and Heinz discovered that gross distortion of tonotopy is the most important contributor to impaired encoding of speech in noise in chinchillas with noise-induced hearing loss.

Noise exposure greatly altered responses of auditory fibers to both vowels and consonants in a spoken sentence. Normally, auditory fibers are driven most strongly by stimulus features with frequencies closest to the fiber's characteristic frequency. In noise-exposed chinchillas, however, low-frequency features were overrepresented, even by fibers with much higher characteristic frequencies. Meanwhile, high-frequency features, which are most informative for speech comprehension, were underrepresented. These effects were exacerbated in the presence of speech-shaped noise.

Importantly, linear mixed-effects modeling revealed that reduction in the ratio between fiber responses at the characteristic frequency and at much lower frequencies—a measure of distorted tonotopy—was the major factor contributing to degraded neural representations of speech. In contrast, broadening of tuning curves had minimal effect on speech representation. Therefore, distorted tonotopy may be a major cause of speech comprehension deficits in individuals with noise-induced hearing loss.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Loss of presenilin (top) causes ApoE (red) to accumulate in the nucleus (cyan) of fibroblasts. Normal cytosolic expression is rescued by reintroducing wild-type presenilin (middle), but not by expressing an AD-linked mutant form of presenilin (bottom). See Islam et al. for details.

Interaction between Two Genes Linked to Alzheimer's Disease

Sadequl Islam, Yang Sun, Yuan Gao, Tomohisa Nakamura, Arshad Ali Noorani, et al.

(see pages 1574–1586)

Alzheimer's disease (AD) is characterized by cognitive decline accompanied by extracellular accumulation of β-amyloid (Aβ) peptides in the brain. Aβ is generated by sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Notably, mutations in APP or presenilin, a component of the γ-secretase complex, cause autosomal dominant forms of AD. But, the vast majority of AD cases are sporadic, and the strongest genetic risk factor for sporadic AD is possession of the ε4 allele of apolipoprotein E (ApoE). ApoE is the primary carrier of lipids in the brain, and it is essential for transferring cholesterol from astrocytes to neurons for use in maintaining synaptic structure. In addition to altering cholesterol transport, the ApoE4 allele has been proposed to increase AD risk by impairing glucose metabolism, disrupting the blood–brain barrier, promoting neuroinflammation, and reducing the clearance of Aβ. The fact that ApoE4 and mutant forms of presenilin and APP all increase accumulation of Aβ is consistent with the hypothesis that Aβ accumulation causes AD. But work by Islam et al. indicates that the overlapping effects of AD-linked genes may extend far beyond Aβ accumulation.

Intracellular ApoE is normally localized predominantly in the cytoplasm, but some is present in the nucleus, where it modulates transcription. In presenilin-deficient mouse embryonic fibroblasts, however, intracellular ApoE was largely restricted to the nucleus, and secretion of ApoE was greatly reduced. Importantly, reintroducing wild-type presenilin after presenilin knockout fully reversed nuclear accumulation and restored secretion of ApoE, whereas expressing AD-linked forms of presenilin only partially rescued these effects. Inhibiting γ-secretase activity also increased nuclear accumulation and reduced secretion of ApoE in fibroblasts, and it produced similar effects in primary astrocytes. Moreover, inhibiting γ-secretase in vivo decreased levels of ApoE in CSF. Finally, plasma levels of ApoE were lower in AD patients carrying mutant presenilin than in healthy control subjects.

These results suggest that mutations in presenilin may promote AD in part by causing ApoE to accumulate in the nucleus, which may lead to aberrant transcriptional regulation, and by reducing ApoE secretion, which may impair delivery of cholesterol from astrocytes to neurons. Further elucidation of pathways affected by altering ApoE trafficking may suggest new approaches for treating both sporadic and familial AD.

Footnotes

  • This Week in The Journal was written by Teresa Esch, Ph.D.

Back to top

In this issue

The Journal of Neuroscience: 42 (8)
Journal of Neuroscience
Vol. 42, Issue 8
23 Feb 2022
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Ed Board (PDF)
Email

Thank you for sharing this Journal of Neuroscience article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
This Week in The Journal
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
This Week in The Journal
Journal of Neuroscience 23 February 2022, 42 (8) 1374; DOI: 10.1523/JNEUROSCI.twij.42.8.2022

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
This Week in The Journal
Journal of Neuroscience 23 February 2022, 42 (8) 1374; DOI: 10.1523/JNEUROSCI.twij.42.8.2022
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Distorted Tonotopy after Noise-Induced Hearing Loss
    • Interaction between Two Genes Linked to Alzheimer's Disease
    • Footnotes
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

  • This Week in The Journal
  • This Week in The Journal
  • This Week in The Journal
Show more This Week in The Journal
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
(JNeurosci logo)
(SfN logo)

Copyright © 2022 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.