Auditory Research publications

Atoh1 overexpression is essential for hair cell (HC) regeneration in the sensory epithelium of mammalian auditory and vestibular organs. However, Atoh1 overexpression alone cannot induce fully mature and functional HCs in the mammalian inner ear. In the current study, we investigated the effect of Atoh1 constitutive overexpression in native HCs by manipulating Atoh1 expression at different developmental stages. We demonstrated that constitutive overexpression of Atoh1 in native vestibular HCs did not affect cell survival but did impair vestibular function by interfering with the subtype differentiation of HCs and hair bundle development. In contrast, Atoh1 overexpression in cochlear HCs impeded their maturation, eventually leading to gradual HC loss in the cochlea and hearing dysfunction. Our study suggests that time-restricted Atoh1 expression is essential for the differentiation and survival of HCs in the inner ear, and this is pivotal for both hearing and vestibular function re-establishment through Atoh1 overexpression-induced HC regeneration strategies.

Phosphatidylglycerol (PG) is a mitochondrial phospholipid required for mitochondrial cristae structure and cardiolipin synthesis. PG must be remodeled to its mature form at the endoplasmic reticulum (ER) after mitochondrial biosynthesis to achieve its biological functions. Defective PG remodeling causes MEGDEL (non-alcohol fatty liver disease and 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like) syndrome through poorly defined mechanisms. Here, we identify LPGAT1, an acyltransferase that catalyzes PG remodeling, as a candidate gene for MEGDEL syndrome. We show that PG remodeling by LPGAT1 at the ER is closely coordinated with mitochondrial transport through interaction with the prohibitin/TIMM14 mitochondrial import motor. Accordingly, ablation of LPGAT1 or TIMM14 not only causes aberrant fatty acyl compositions but also ER retention of newly remodeled PG, leading to profound loss in mitochondrial crista structure and respiration. Consequently, genetic deletion of the LPGAT1 in mice leads to cardinal features of MEGDEL syndrome, including 3-methylglutaconic aciduria, deafness, dilated cardiomyopathy, and premature death, which are highly reminiscent of those caused by TIMM14 mutations in humans.

This study investigated word recognition for sentences temporally filtered within and across acoustic–phonetic segments providing primarily vocalic or consonantal cues. Amplitude modulation was filtered at syllabic (0–8 Hz) or slow phonemic (8–16 Hz) rates. Sentence-level modulation properties were also varied by amplifying or attenuating segments. Participants were older adults with normal or impaired hearing. Older adult speech recognition was compared to groups of younger normal-hearing adults who heard speech unmodified or spectrally shaped with and without threshold matching noise that matched audibility to hearing-impaired thresholds. Participants also completed cognitive and speech recognition measures. Overall, results confirm the primary contribution of syllabic speech modulations to recognition and demonstrate the importance of these modulations across vowel and consonant segments. Group differences demonstrated a hearing loss–related impairment in processing modulation-filtered speech, particularly at 8–16 Hz. This impairment could not be fully explained by age or poorer audibility. Principal components analysis identified a single factor score that summarized speech recognition across modulation-filtered conditions; analysis of individual differences explained 81% of the variance in this summary factor among the older adults with hearing loss. These results suggest that a combination of cognitive abilities and speech glimpsing abilities contribute to speech recognition in this group.

Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their transformation to mediate flexibility of fear-induced defensive behaviors remain largely unknown. Here, we report that distinct neuronal populations in mouse anterior cingulate cortex (ACC) encode safety status by selectively responding under different contexts of auditory threats, with one preferably activated when an animal staysing in a self-deemed safe zone and another specifically activated in more dangerous environmental settings that led to escape behavior. The safety-responding neurons preferentially target the zona incerta (ZI), which suppresses the superior colliculus (SC) via its GABAergic projection, while the danger-responding neurons preferentially target and excite SC. These distinct corticofugal pathways antagonistically modulate SC responses to threat, resulting in context-dependent expression of fear reactions. Thus, ACC serves as a critical node to encode safety/danger assessment and mediate behavioral flexibility through differential top-down circuits.

Williams syndrome is a developmental disorder caused by a microdeletion entailing the loss of a single copy of 25-27 genes on chromosome 7q11.23. Patients suffer from cardiovascular and neuropsychological symptoms. Structural abnormalities of the cardiovascular system in Williams syndrome have been attributed to the hemizygous loss of the elastin ( ELN ) gene. In contrast, the neuropsychological consequences of Williams syndrome, including sensorimotor deficits, hypersociability and cognitive impairments, have been mainly attributed to altered expression of transcription factors like LIMK1 , GTF2I and GTF2IRD1 , while the potential impact of altered cerebrovascular function has been largely overlooked. To study the relationship between Williams syndrome mutations and vascularization of both the heart and brain, we generated a mouse model carrying a relatively long microdeletion (LD) that includes the Ncf1 gene, thereby minimizing the confounding impact of hypertension. LD mice had elongated and tortuous aortas but, unlike Eln haploinsufficient mice, showed no signs of structural cardiac hypertrophy. Remarkably, LD mice also displayed structural abnormalities in coronary and brain vessels, including disorganized extracellular matrices. Importantly, LD mice faithfully replicated both cardiovascular and neuropsychological symptoms observed in patients. The phenotype was even more comprehensive than former models, with structure-function correlations evident in aberrant auditory and motor behaviors resembling those in patients with Williams syndrome. Together, our findings suggest that not only cardiovascular but also neuropsychological symptoms in Williams syndrome may be driven in part by vascular abnormalities affecting both heart and brain. Significance Statement Williams syndrome is caused by microdeletion of 25-27 genes on chromosome 7q11.23, resulting in cardiovascular and neuropsychological symptoms. It remains unclear how the affected genes interact and whether cardiovascular deficits influence brain function. We developed and characterized a mouse model with the longest Williams syndrome microdeletion to date. This model reveals interactions between genes that can be compensatory or additive: haploinsufficiency of Ncf1 may counteract the cardiac hypertrophy caused by Eln deletion, while vascular defects that are potentially due to Eln haploinsufficiency extend to the brain and may worsen neuropsychological symptoms. Our findings support the hypothesis that structural vascular deficits putatively contribute to both cardiac and cognitive phenotypes in Williams syndrome, opening new avenues for understanding and treating this syndrome.

Mice are increasingly used as models of human-acquired neurological or neurodevelopmental conditions, such as autism, schizophrenia, and Alzheimer’s disease. All these conditions involve central auditory processing disorders, which have been little investigated despite their potential for providing interesting insights into the mechanisms behind such disorders. Alterations of the auditory steady-state response to 40 Hz click trains are associated with an imbalance between neuronal excitation and inhibition, a mechanism thought to be common to many neurological disorders. Here, we demonstrate the value of presenting click trains at various rates to mice with chronically implanted pins above the inferior colliculus and the auditory cortex for obtaining easy, reliable, and long-lasting access to subcortical and cortical complex auditory processing in awake mice. Using this protocol on a mutant mouse model of autism with a defect of the Shank3 gene, we show that the neural response is impaired at high click rates (above 60 Hz) and that this impairment is visible subcortically—two results that cannot be obtained with classical protocols for cortical EEG recordings in response to stimulation at 40 Hz. These results demonstrate the value and necessity of a more complete investigation of central auditory processing disorders in mouse models of neurological or neurodevelopmental disorders.

In tonal languages, which are spoken by nearly one-third of the world’s population, speakers precisely control the tension of vocal folds in the larynx to modulate pitch in order to distinguish words with completely different meanings. The specific pitch trajectories for a given tonal language are called lexical tones. Here, we used high-density direct cortical recordings to determine the neural basis of lexical tone production in native Mandarin-speaking participants. We found that instead of a tone category-selective coding, local populations in the bilateral laryngeal motor cortex (LMC) encode articulatory kinematic information to generate the pitch dynamics of lexical tones. Using a computational model of tone production, we discovered two distinct patterns of population activity in LMC commanding pitch rising and lowering. Finally, we showed that direct electrocortical stimulation of different local populations in LMC evoked pitch rising and lowering during tone production, respectively. Together, these results reveal the neural basis of vocal pitch control of lexical tones in tonal languages.

The human auditory system extracts rich linguistic abstractions from speech signals. Traditional approaches to understanding this complex process have used linear feature-encoding models, with limited success. Artificial neural networks excel in speech recognition tasks and offer promising computational models of speech processing. We used speech representations in state-of-the-art deep neural network (DNN) models to investigate neural coding from the auditory nerve to the speech cortex. Representations in hierarchical layers of the DNN correlated well with the neural activity throughout the ascending auditory system. Unsupervised speech models performed at least as well as other purely supervised or fine-tuned models. Deeper DNN layers were better correlated with the neural activity in the higher-order auditory cortex, with computations aligned with phonemic and syllabic structures in speech. Accordingly, DNN models trained on either English or Mandarin predicted cortical responses in native speakers of each language. These results reveal convergence between DNN model representations and the biological auditory pathway, offering new approaches for modeling neural coding in the auditory cortex.

Objective We compared the histological changes and hearing restoration during the healing of acute total tympanic membrane (TM) perforations between Sprague–Dawley (SD) rats with and without excision of the mallear handle. Materials and methods Bilateral, acute, and total TM perforations were created in 36 male SD rats. The mallear handle was preserved in the left ear (handle‐preserved ear [HPE]) and excised from the right ear (handle‐excised ear [HEE]). Endoscopical examination, auditory brainstem response (ABR) thresholds, histopathological, and scanning electron microscope (SEM) analysis were performed. Results Endoscopic photographs showed that all perforations in the 18 SD rats were closed. The mean closure times were 6.83 ± 0.85 and 8.50 ± 0.71 days in the HPE and HEE groups, respectively ( p < .001). SEM images showed radial arrangement of fiber bundles in a single direction in HPEs, although normal arrangement was not achieved. In contrast, HEEs showed disorganized arrangement. At 1 month after perforation closure, the ABR thresholds at high frequencies were significantly higher in the HEE group than in the HPE group ( p = .029 and p = .017 for 16 and 32 kHz, respectively). Additionally, the changes in ABR threshold were significantly different at high frequencies ( p = .011 and p = .017 for 16 and 32 kHz, respectively) before and 1 month after perforation closure between the HPE and HEE groups, although the differences were not statistically significant at the remaining frequencies. Conclusion Although the malleus handle may not affect the closure of total perforation in SD rats, it contributes to accelerate the perforation closure by possible guide the migration of proliferative epithelial cell on the upper halves of the annulus. Additionally, resection of the malleus handle impairs high frequency hearing recovery following spontaneous closure of the TM.

Objective The mechanism by which migraines produce inner ear-related symptoms is not well understood. Previous studies have found that the latency of auditory brainstem response (ABR) in animal models of migraine has changed, but the threshold has not changed significantly. Therefore, it is necessary to establish a better animal model with both migraine and hearing loss to explore the relationship between migraine and auditory function deeply. Methods In this study, the rat model of migraine was induced by postauricular injection of nitroglycerin (NTG), and the effect on the auditory function of the inner ear was explored by comparing with intraperitoneal injection of nitroglycerin. The rats were given the drug repeatedly on alternate days, a total of 5 dosing, with the body weight monitored during the drug administration. The tactile threshold of the rats' forepaw was measured using von-Frey filaments and auditory function was assessed by ABR. Results The results showed that the baseline tactile threshold of rats gradually decreased during the modeling process, and hyperalgesia appeared. Postauricular injection of NTG did not affect the weight gain of rats, while intraperitoneal injection of NTG showed slow or even negative weight gain. The ABR threshold of Click, 4 and 8 kHz of postauricular NTG injection rats increased, the latency was prolonged, and the ABR threshold in the right ear was higher than that in the left ear. Conclusions We demonstrated that postauricular injection of nitroglycerin may be safer and more effective than intraperitoneal injection of nitroglycerin in the process of creating rat migraine model without affecting the weight gain. Postauricular injection of nitroglycerin has more damage to the auditory function of rats. Therefore, the migraine model rat induced by postauricular injection of nitroglycerin may be a new model of cochlear migraine.

The relative importance or saliency of sensory inputs depend on the animal’s environmental context and the behavioural responses to these same inputs can vary over time. Here we show how freely moving rats, trained to discriminate between deviant tones embedded in a regular pattern of repeating stimuli and different variations of the classic oddball paradigm, can detect deviant tones, and this discriminability resembles the properties that are typical of neuronal adaptation described in previous studies. Moreover, the auditory brainstem response (ABR) latency decreases after training, a finding consistent with the notion that animals develop a type of plasticity to auditory stimuli. Our study suggests the existence of a form of long-term memory that may modulate the level of neuronal adaptation according to its behavioural relevance, and sets the ground for future experiments that will help to disentangle the functional mechanisms that govern behavioural habituation and its relation to neuronal adaptation.

In the receptor organs of the inner ear and lateral line, sensory hair cells detect mechanical stimuli such as sounds, accelerations, and water movements. In each instance a stimulus deflects the hair bundle, a hair cell’s mechanically sensitive organelle. The bundle pivots upon the cell’s apical surface, which includes an actin meshwork called the cuticular plate and is surrounded by a ring of filamentous actin and non-muscle myosin II (NM2). Myosin regulatory light chain (RLC) is expressed at the apical surfaces of hair cells and RLC is additionally found in hair bundles. NM2 and the phosphorylation of RLC by myosin light chain kinase (MLCK) have earlier been shown to regulate the sizes and shapes of hair cells’ apical surfaces. We have found that inhibitors of NM2 and MLCK reduce the stiffness of hair bundles from the bullfrog’s sacculus. Moreover, MLCK inhibition inhibits the spontaneous oscillation of hair bundles and increases the resting open probability of transduction channels. In addition, MLCK inhibition elevates hearing thresholds in mice. We conclude that NM2 and the phosphorylation of RLC modulate slow adaptation and thereby help to set the normal operating conditions of hair bundles. Statement of significance Sensory hair cells play a key role in mechanoelectrical transduction by the inner ear and lateral-line system. To detect stimuli such as sounds and accelerations, hair cells use an active process to amplify their mechanical inputs. Although amplification is accomplished in part by the activity of the mechanosensitive hair bundles, the molecular mechanism of the active process remains uncertain. The present study shows that non-muscle myosin II (NM2) and the phosphorylation of myosin regulatory right chains (RLC) by myosin light chain kinase (MLCK) regulate the stiffness and spontaneous oscillation of hair bundles as well as the resting open probability of mechanotransduction channels. The results implicate myosin motors in the control of the active process of hair cells.

Background Vestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive function, and processing speed among others. Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems; however, individuals also experience measurable deficits in basic decision-making, short-term memory, concentration, spatial cognition, and depression. These suggest central mechanisms of impairment are associated with vestibular disorders; therefore, we directly tested this hypothesis using both an auditory and visual decision-making task of varying difficulty levels in our model of SSCD. Methods Adult Mongolian gerbils ( n = 33) were trained on one of four versions of a Go-NoGo stimulus presentation rate discrimination task that included standard (“easy”) or more difficult (“hard”) auditory and visual stimuli. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Animals with persistent circling or head tilt were excluded to minimize effects from acute vestibular injury. Testing recommenced at postoperative day 5 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out. Results Behavioral data (d-primes) were compared between preoperative performance (training day 8–10) and postoperative days 6–8 and 13–15. Behavioral performance was measured during the peak of SSCD induced ABR and c + VEMP impairment and the return towards baseline as the dehiscence began to resurface by osteoneogenesis. There were significant differences in behavioral performance (d-prime) and its behavioral components (Hits, Misses, False Alarms, and Correct Rejections). These changes were highly correlated with persistent deficits in c + VEMPs at the end of training (postoperative day 15). The controls demonstrated additional learning post procedure that was absent in the SSCD group. Conclusion These results suggest that aberrant asymmetric vestibular output results in decision-making impairments in these discrimination tasks and could be associated with the other cognitive impairments resulting from vestibular dysfunction.

Objective Cognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word‐finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word‐finding difficulty in patients, and if so, through which cognitive mechanism(s). Methods Twenty‐three patients undergoing intracranial monitoring for drug‐resistant epilepsy participated in multiple tasks involving word production (auditory naming, short‐term verbal free recall, repetition) to probe word‐finding difficulty across different cognitive domains. We compared behavioral performance between trials with versus without interictal discharges across six major brain areas and adjusted for intersubject differences using mixed‐effects models. We also evaluated for subjective word‐finding difficulties through retrospective chart review. Results Subjective word‐finding difficulty was reported by the majority (79%) of studied patients preoperatively. During intracranial recordings, interictal epileptiform discharges (IEDs) in the medial temporal lobe were associated with long‐term lexicosemantic memory impairments as indexed by auditory naming ( p = .009), in addition to their established impact on short‐term verbal memory as indexed by free recall ( p = .004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task ( p = .016 and p = .018), as well as phonological working memory impairments as indexed by repetition reaction time ( p = .002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task. Significance IEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word‐finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes, which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.

Background: Hearing loss is a global health issue and its etiopathologies involve complex molecular pathways. The ubiquitin-proteasome system has been reported to be associated with cochlear development and hearing loss. The gene related to anergy in lymphocytes ( GRAIL ), as an E3 ubiquitin ligase, has not, as yet, been examined in aging-related and noise-induced hearing loss mice models. Methods: This study used wild-type (WT) and GRAIL knockout (KO) mice to examine cochlear hair cells and synaptic ribbons using immunofluorescence staining. The hearing in WT and KO mice was detected using auditory brainstem response. Gene expression patterns were compared using RNA-sequencing to identify potential targets during the pathogenesis of noise-induced hearing loss in WT and KO mice. Results: At the 12-month follow-up, GRAIL KO mice had significantly less elevation in threshold level and immunofluorescence staining showed less loss of outer hair cells and synaptic ribbons in the hook region compared with GRAIL WT mice. At days 1, 14, and 28 after noise exposure, GRAIL KO mice had significantly less elevation in threshold level than WT mice. After noise exposure, GRAIL KO mice showed less loss of outer hair cells in the cochlear hook and basal regions compared with WT mice. Moreover, immunofluorescence staining showed less loss of synaptic ribbons in the hook regions of GRAIL KO mice than of WT mice. RNA-seq analysis results showed significant differences in C-C motif chemokine ligand 19 ( CCL19 ), C-C motif chemokine ligand 21 ( CCL21 ), interleukin 25 ( IL25 ), glutathione peroxidase 6 ( GPX6 ), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 ( NOX1 ) genes after noise exposure. Conclusion: The present data demonstrated that GRAIL deficiency protects against aging-related and noise-induced hearing loss. The mechanism involved needs to be further clarified from the potential association with synaptic modulation, inflammation, and oxidative stress.

Hearing loss is the most common form of sensory deficit. It occurs predominantly due to hair cell (HC) loss. Mammalian HCs are terminally differentiated by birth, making HC loss challenging to replace. Here, we show the pharmacogenetic downregulation of Cldn9 , a tight junction protein, generates robust supernumerary inner HCs (IHCs) in mice. The ectopic IHC shared functional and synaptic features akin to typical IHCs and were surprisingly and remarkably preserved for at least fifteen months >50% of the mouse’s life cycle. In vivo , Cldn9 knockdown using shRNA on postnatal days (P) P2-7 yielded analogous functional ectopic IHCs that were equally durably conserved. The findings suggest that Cldn9 levels coordinate embryonic and postnatal HC differentiation, making it a viable target for altering IHC development pre- and post-terminal differentiation.

The human brain extracts meaning using an extensive neural system for semantic knowledge. Whether broadly distributed systems depend on or can compensate after losing a highly interconnected hub is controversial. We report intracranial recordings from two patients during a speech prediction task, obtained minutes before and after neurosurgical treatment requiring disconnection of the left anterior temporal lobe (ATL), a candidate semantic knowledge hub. Informed by modern diaschisis and predictive coding frameworks, we tested hypotheses ranging from solely neural network disruption to complete compensation by the indirectly affected language-related and speech-processing sites. Immediately after ATL disconnection, we observed neurophysiological alterations in the recorded frontal and auditory sites, providing direct evidence for the importance of the ATL as a semantic hub. We also obtained evidence for rapid, albeit incomplete, attempts at neural network compensation, with neural impact largely in the forms stipulated by the predictive coding framework, in specificity, and the modern diaschisis framework, more generally. The overall results validate these frameworks and reveal an immediate impact and capability of the human brain to adjust after losing a brain hub.

Pathological conditions in cochlea, such as ototoxicity, acoustic trauma, and age-related cochlear degeneration, induce cell death in the organ of Corti and degeneration of the spiral ganglion neurons (SGNs). Although macrophages play an essential role after cochlear injury, its role in the SGNs is limitedly understood. We analyzed the status of macrophage activation and neuronal damage in the spiral ganglion after kanamycin-induced unilateral hearing loss in mice. The number of ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages increased 3 days after unilateral kanamycin injection. Macrophages showed larger cell bodies, suggesting activation status. Interestingly, the number of activating transcription factor 3 (ATF3)-positive-neurons, an indicator of early neuronal damage, also increased at the same timing. In the later stages, the number of macrophages decreased, and the cell bodies became smaller, although the number of neuronal deaths increased. To understand their role in neuronal damage, macrophages were depleted via intraperitoneal injection of clodronate liposome 24 h after kanamycin injection. Macrophage depletion decreased the number of ATF3-positive neurons at day 3 and neuronal death at day 28 in the spiral ganglion following kanamycin injection. Our results suggest that suppression of inflammation by clodronate at early timing can protect spiral ganglion damage following cochlear insult.

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.

Background Highly specialized cells with self-renewal and differentiation potentials are known to as stem cells. These cells can keep their stemness or develop into more specialized cells. Mesenchymal stem cell (MSC)-based cell treatment has caught researchers' interest due to its lack of ethical problems, simplicity of isolation, and abundance. The use of stem cell treatment in regenerative medicine has recently been a subject of great interest. In vitro and in vivo, MSCs have been shown to have anti-inflammatory and immunomodulatory properties. The ability of MSCs to decrease T-cell proliferation and reduce T-cell functioning is responsible for their potent immunosuppressive effects. They possess potential to home to injury site and stimulate indigenous cells to repair and rebuild it, despite their homing ability delivering the stem cell to the anatomically complex area such as inner is still remains as challenge. Studies on enhancing the delivery of stem cells has been emerging. Method The Superparamagnetic iron oxide nanoparticles (SPION) with an iron oxide-based nanoparticle cluster core covered with PLGA-Cy5.5 has been developed. To allow PCS nanoparticles to be transported into MSCs by endocytosis, we modified the nanoparticles for internalization. Nanoparticle labeled mesenchymal stem cells are administered in ototoxic mouse model with or without magnetic field. Results As an outcome, when compared to the control groups, the intratympanic administration with magnet group had the most cells in the brain, followed by the liver, cochlea, and kidney. The magnetic interaction between the produced PCS (poly clustered superparamagnetic iron oxide) nanoparticles and MSCs may increase stem cell delivery effectively. In a variety of experimental models examining cell responsiveness in vitro and in situ, the potential use of SPION to increase the spatial control of stem cells by the application of magnetic fields was examined. The application of the magnetic field has significantly increased the number of cells that migrate toward the area of magnet application in vitro. However, in in vivo settings the quantification of the effect of magnetic field was yet solved. Conclusion The visualization of delivered MSCs, as well as quantitative and qualitative analysis of the processes, will contribute in the formulation of an assessment system for a powerful delivery system in the inner ear, which will aid in the treatment of hearing loss