The Cochlear Implant in Action: Molecular Changes Induced in the Rat Central Auditory System

Hildebrandt

Birkenhäger

et al. 2018

Front. Cell. Neurosci.

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Neuron–glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs). The effectiveness of stimulation was verified by electrically evoked ABRs as well as immunocytochemistry and in situ hybridization for the immediate early gene product Fos on sections through the auditory midbrain containing the inferior colliculus (IC). Whereas hearing-experienced animals showed a tonotopically restricted Fos response in the IC contralateral to electrical intracochlear stimulation, Fos-positive neurons were found almost throughout the contralateral IC in deaf animals. In deaf rats, the Fos response was accompanied by a massive increase of GFAP indicating astrocytic hypertrophy, and a local activation of microglial cells identified by IBA1. These glia responses led to a noticeable increase of neuron–glia approximations. Moreover, staining for the GABA synthetizing enzymes GAD65 and GAD67 rose significantly in neuronal cell bodies and presynaptic boutons in the contralateral IC of deaf rats. Activation of neurons and glial cells and tissue re-composition were in no case accompanied by cell death as would have been apparent by a Tunel reaction. These findings suggest that growth and activity of glial cells is crucial for the local adjustment of neuronal inhibition to neuronal excitation.

Section: Methodsmentioning

confidence: 99%

Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation

Hildebrandt

Birkenhäger

et al. 2018

Front. Cell. Neurosci.

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“…Various lines of animal experimentation make such a critical period hypothesis plausible, including immunohistochemical studies that have shown degraded tonotopic organization ( Rosskothen-Kuhl and Illing, 2012 ; Rauch et al, 2016 ) and changes in stimulation-induced molecular, cellular, and morphological properties of the auditory pathway of neonatally deafened (ND) CI rats ( Illing and Rosskothen-Kuhl, 2012 ; Rosskothen-Kuhl and Illing, 2012 ; Jakob et al, 2015 ; Rauch et al, 2016 ; Rosskothen-Kuhl et al, 2018 ). Additional studies demonstrate that abnormal sensory input during early development can alter ITD tuning curves in key brainstem nuclei of gerbils ( Seidl and Grothe, 2005 ; Beiderbeck et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Microsecond interaural time difference discrimination restored by cochlear implants after neonatal deafness

Buck

et al. 2021

eLife

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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.

“…By the time these patients are old enough to receive implants, they may already have missed out on the formative sensory input needed to develop the brain circuitry required for binaural processing with microsecond precision. This possibility seems particularly plausible given that immunohistochemical studies have shown that the tonotopic organization is degraded [15,16] and that stimulation-induced molecular, morphological, and electrophysiolological plasticity is altered in neonatally deafened rats compared to CI-stimulated rats with normal auditory development [15][16][17][18][19]. Furthermore, it has been shown that early acoustic experience shapes ITD tuning curves in key brainstem nuclei of gerbils [20], probably by shaping the precise timing of inhibitory inputs into superior olivary nuclei [20,21].…”

mentioning

confidence: 99%

Microsecond Interaural Time Difference Discrimination Restored by Cochlear Implants After Neonatal Deafness

Buck

et al. 2018

Preprint

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Cochlear implants (CIs) can restore a high degree of functional hearing in deaf patients but enable only poor spatial hearing or hearing in noise. Early deaf CI users are essentially completely insensitive to interaural time differences (ITDs). A dearth of binaural experience during an early critical period is often blamed for these shortcomings. However, here we show that neonatally deafened rats which are fitted with binaural CIs in early adulthood are highly sensitive to ITDs immediately after implantation. Under binaural synchronized stimulation they can be trained to localize ITDs with essentially normal behavioral thresholds near 50 μs. This suggests that the deficits seen in human patients are unlikely to be caused by lack of experience during their period of deafness. It may instead be due to months or years of CI stimulation with inappropriate binaural parameters provided by CI processors which do not provide sub-millisecond temporal fine structure of sounds . 3 33 34 35 36 37 38 39 40 41 42 43 44 45 The World Health Organization reports that about 466 million people suffer from disabling hearing loss, making it the most common sensory impairment of our age. For people with severe to profound sensorineural hearing loss, cochlear implants (CIs) can be enormously beneficial, quite routinely allowing near normal spoken language acquisition, particularly when CI implantation takes place early in life [1]. Never the less the performance of CI users remains variable, and even in the best cases falls short of natural hearing.Good speech understanding in multi-sound environment requires the ability to separate speech from background, which relies in part on a phenomenon known as "spatial release from masking". This relies on the brain's ability to process binaural spatial cues, including interaural level and interaural time differences (ILDs/ITDs) [2]. To benefit from binaural cues in everyday life, bilateral cochlear implantation is becoming increasingly common for deaf patients [3][4][5] . However, even binaural CI patients perform much below the level of normal listeners in sound localization or auditory scene analysis tasks, particularly when multiple sound sources are present [6,7]. The parameters that would allow CI patients to derive maximum benefits from binaural spatial cues are still only partially understood. A number of technical problems (see [8], chapter 6) limit the fidelity with which CIs can encode binaural cues, particularly ITDs. The fact that contemporary CI speech processors were originally designed for monaural, rather than binaural, hearing likely contributes the observed deficits in ITD performance of bilateral CI users [3]. Standard CI processors provide pulsatile stimulation which is not locked to the temporal fine structure of the incoming sounds, and the timing of the electrical pulses is not synchronized between both ears, which makes these devices fundamentally incapable of encoding sub-millisecond binaural time structure. To be useful, ITDs as small as a few tens ...