Microsecond interaural time difference discrimination restored by cochlear implants after neonatal deafness
Abstract
Spatial hearing in cochlear implant (CI) patients remains a major challenge with many early deaf users reported to have no measurable sensitivity to interaural time differences (ITDs). Deprivation of binaural experience during an early critical period is often hypothesized to be the cause of this shortcoming. However, we show that neonatally deafened (ND) rats provided with precisely synchronized CI stimulation in adulthood can be trained to lateralize ITDs with essentially normal behavioral thresholds near 50 μs. Furthermore, comparable ND rats show high physiological sensitivity to ITDs immediately after binaural implantation in adulthood. Our result that ND CI rats achieved very good behavioral ITD thresholds while prelingually deaf human CI patients often fail to develop a useful sensitivity to ITD raises urgent questions concerning the possibility that shortcomings in technology or treatment, rather than missing input during early development, may be behind the usually poor binaural outcomes for current CI patients.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Data have been deposited to Dryad, under the DOI 10.5061/dryad.573n5tb6d.
-
Behavioral and ephys data of research paperDryad Digital Repository, doi:10.5061/dryad.573n5tb6d.
Article and author information
Author details
Funding
Deutscher Akademischer Austauschdienst (P.R.I.M.E. - Postdoctoral Researchers International Mobility Experience,REA grant agreement n 605728)
- Nicole Rosskothen-Kuhl
Hong Kong General Research Fund (Hong Kong General Research Fund (11100219))
- Jan W H Schnupp
Deutsche Forschungsgemeinschaft (Cluster of Excellence BrainLinks-BrainTools,Grant number EXC1086)
- Nicole Rosskothen-Kuhl
Taube Kinder lernen hoeren e.V.
- Nicole Rosskothen-Kuhl
Hong Kong (Medical Research Fund (06172296))
- Jan W H Schnupp
Shenzhen Science and Innovation Fund (Shenzhen Science and Innovation Fund (JCYJ20180307124024360))
- Jan W H Schnupp
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 involving experimental animals reported here were approved by the Department of Health of Hong Kong (#16-52 DH/HA&P/8/2/5) or Regierungspräsidium Freiburg (#35-9185.81/G-17/124), as well as by the appropriate local ethical review committee. All surgery was performed under ketamine and xylazine anesthesia, and every effort was made to minimize suffering.
Copyright
© 2021, Rosskothen-Kuhl 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
-
- 1,597
- views
-
- 225
- downloads
-
- 29
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
The brain is organized into systems and networks of interacting components. The functional connections among these components give insight into the brain's organization and may underlie some cognitive effects of aging. Examining the relationship between individual differences in brain organization and cognitive function in older adults who have reached oldest old ages with healthy cognition can help us understand how these networks support healthy cognitive aging. We investigated functional network segregation in 146 cognitively healthy participants aged 85+ in the McKnight Brain Aging Registry. We found that the segregation of the association system and the individual networks within the association system [the fronto-parietal network (FPN), cingulo-opercular network (CON) and default mode network (DMN)], has strong associations with overall cognition and processing speed. We also provide a healthy oldest-old (85+) cortical parcellation that can be used in future work in this age group. This study shows that network segregation of the oldest-old brain is closely linked to cognitive performance. This work adds to the growing body of knowledge about differentiation in the aged brain by demonstrating that cognitive ability is associated with differentiated functional networks in very old individuals representing successful cognitive aging.
-
- Cell Biology
- Neuroscience
The emergence of Aβ pathology is one of the hallmarks of Alzheimer’s disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC function in neurons. Here, we examined NPC and nucleoporin (NUP) distribution and nucleocytoplasmic transport using a mouse model of AD (AppNL-G-F/NL-G-F) that expresses Aβ in young animals. Our studies revealed that a time-dependent accumulation of intracellular Aβ corresponded with a reduction of NPCs and NUPs in the nuclear envelope which resulted in the degradation of the permeability barrier and inefficient segregation of nucleocytoplasmic proteins, and active transport. As a result of the NPC dysfunction App KI neurons become more vulnerable to inflammation-induced necroptosis – a programmed cell death pathway where the core components are activated via phosphorylation through nucleocytoplasmic shutting. Collectively, our data implicates Aβ in progressive impairment of nuclear pore function and further confirms that the protein complex is vulnerable to disruption in various neurodegenerative diseases and is a potential therapeutic target.