Structural and functional diversity of mitochondria in vestibular/cochlear hair cells and vestibular calyx afferents

Lysakowski, Anna; Govindaraju, Aravind Chenrayan; Raphael, Robert M.

doi:10.1016/j.heares.2022.108612

Cited by 5 publications

(3 citation statements)

References 148 publications

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“…Our results show that hair cells expressing Tmem135 are lost in the aging FUN025 mouse. Hair cells are well documented to have elevated energetic demand and thought to have a high concentration of mitochondria within their cytoplasm (Fettiplace R et al, 2019; Lysakowski et al, 2022). Given the functions of TMEM135 in regulating mitochondrial dynamics (Lee et al, 2016) and lipid metabolism in other cell types (Landowski et al, 2022), we speculate that TMEM135 is similarly critical for mitochondrial function in these highly metabolically-active cochlear cells.…”

Section: Discussionmentioning

confidence: 99%

A Mutation inTmem135Causes Progressive Sensorineural Hearing Loss

Kim,

Simms,

Behnammanesh

et al. 2024

Preprint

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Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135FUN025/FUN025 (FUN025) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

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Section: Discussionmentioning

confidence: 99%

A Mutation inTmem135Causes Progressive Sensorineural Hearing Loss

Kim,

Simms,

Behnammanesh

et al. 2024

Preprint

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“…Because the LPR is situated at the site of adjacency of large and small otoconia in the utricle, movement of gel due to velocity change is maximized. In the saccule, the LPR is under the middle of the striola [ 52 , 65 , 66 ].…”

Section: Significance Of the Location Of The Line Of Polarity Reversa...mentioning

confidence: 99%

A New Perspective to Interpret How the Vestibular Efferent System Correlates the Complexity of Routine Balance Maintenance with Management of Emergency Fall Prevention Strategies

Longridge,

Mallinson

2024

Audiology Research

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Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and it can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information simultaneously transmitted to the maculae with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system causes macular otolithic membrane movement through the STO, which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

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“…Noise-induced down-regulation of calretinin would alter the dynamics of the intracellular free Ca 2+ in calyx-only afferents, which in turn would influence the activity of calcium-dependent K+ channels, HCN channel via cAMP, KCNQ K+ channels via calmodulin, and efferent modulation via G-protein coupled mechanism (Holt et al, 2017(Holt et al, , 2015Lee et al, 2017;Meredith et al, 2011;Seseña et al, 2014;Ventura and Kalluri, 2019). The calix-only afferents contain calbindin, calcium pumps, and many mitochondria in addition to calretinin (Lysakowski et al, 2022;Lysakowski and Goldberg, 1997), indicating that their intracellular free Ca 2+ must be intricately regulated through mechanisms having different spatiotemporal dynamics. We found a robust correlation between the number of CR+ calyces and a change in head stability and orientation.…”

Section: Noise Exposure Affects the Expression Of Calcium-binding Pro...mentioning

confidence: 99%

Noise-induced changes in rat head stability and orientation correlate with dysfunction of otolith irregular afferents

Niwa,

Bauer,

Anderson

et al. 2023

Preprint

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Exposure to intense noise damages both the cochlea and vestibular end organs. Our group previously reported attenuated vestibular short-latency evoked potentials (VsEP) and reduced numbers of calretinin-positive (CR+) calyces in the saccule following noise exposure. Here, we examined rats’ resting head orientation with respect to gravity as well as head stability following a 4-hour exposure to 120 dB SPL noise. We also assessed how behavioral changes are related to changes in VsEP waveforms and calretinin expression in the otoliths to elucidate potential underlying mechanisms. We found significant delays in the VsEP N1 and P2 peak latencies and significant reductions in the N2P3 amplitudes following noise exposure. The number of CR+ calyces in both saccule and utricle were also significantly reduced. The size of the reduction in N2P3 amplitude was significantly correlated to the number of CR+ calyces in the utricle, but not to the saccule. Animals with larger delays in N1 peak latency and/or smaller numbers of CR+ calyces in the utricle following noise showed significant decreases in the average speed of y-axis rotational head motion, while those with smaller changes showed significant increases. In addition, animals with larger noise-induced changes held their heads motionless longer following noise exposure. We hypothesize that noise exposure is inherently destructive to an animal’s head stability and thereby manifests as an increase in average head speed in mildly to moderately affected animals. But when the damage was large enough, animals exhibited reduced duration and head motion speed as a behavioral adaptation. The noise exposure also significantly altered the pitch angle of head orientation in animals who had the smallest number of CR+ calyces in the saccule, suggesting that saccular irregular afferents, including those that are CR+, are critical in control of head and body posture.

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Structural and functional diversity of mitochondria in vestibular/cochlear hair cells and vestibular calyx afferents

Cited by 5 publications

References 148 publications

A Mutation inTmem135Causes Progressive Sensorineural Hearing Loss

A Mutation inTmem135Causes Progressive Sensorineural Hearing Loss

A New Perspective to Interpret How the Vestibular Efferent System Correlates the Complexity of Routine Balance Maintenance with Management of Emergency Fall Prevention Strategies

Noise-induced changes in rat head stability and orientation correlate with dysfunction of otolith irregular afferents

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