Yige Li

All Publications

• Celf4 Regulates Excitability of Bushy Cells in the Cochlear Nucleus of the Mouse Brainstem. Cellular and molecular neurobiology Li, Y., Qiu, S., Wang, F., Bi, Z., Liu, Z., He, Y., Li, G. L. 2026; 46 (1)

  Abstract

  The CUGBP Elav-like family 4 (CELF4), an RNA-binding protein, is dynamically expressed in spiral ganglion neurons (SGNs) in the cochlea over development, but how Celf4 is involved in regulating hearing functions is poorly understood. In this study, we generated a Celf4± mouse line and examined changes in the first two synapses along the auditory pathways. Firstly, we found that hearing functions were largely intact in Celf4± mice, with exception of reduced amplitude for Wave II of auditory brainstem responses (ABRs) and increased delays for Wave II and IV, both in case of 4 kHz only. Secondly, we found that counts of inner and outer hair cells (IHCs and OHCs) and SGNs remained unchanged in Celf4± mice, and that the number and function of ribbon synapses between IHCs and SGNs were comparable between WT and Celf4± mice. Lastly, function of the endbulb of Held synapse, formed between auditory nerve fibers (ANFs) of SGNs and bushy cells in the cochlear nucleus, was significantly altered in Celf4± mice. Specifically, synaptic vesicle release was subtly reduced, and excitability of bushy cells was significantly dampened, likely due to a hyperpolarized resting membrane potential. Furthermore, we found that spike kinetics was significantly faster in Celf4± bushy cells, likely caused by a larger fast-inactivating A-type potassium current (IA) found in these cells. In conclusion, we found that Celf4 haploinsufficiency altered transmission at the endbulb of Held synapses in the cochlear nucleus in a significant and multifaceted manner, revealing the roles of Celf4 in regulating hearing functions.

  View details for DOI 10.1007/s10571-026-01732-8

  View details for PubMedID 42029780

  View details for PubMedCentralID PMC13243167

• Cochlear Amplification Modulates Synaptic Transmission at the Endbulb of Held Synapse in the Cochlear Nucleus. The Journal of neuroscience : the official journal of the Society for Neuroscience Wang, F., Li, Y., Li, G. L. 2026; 46 (12)

  Abstract

  In the mammalian cochlea upon acoustic stimulation, outer hair cells (OHCs) push and pull the basilar membrane, amplifying its vibration and therefore expanding the dynamic range of hearing. As a result, spiking patterns in auditory nerve fibers (ANFs) are believed to be significantly different, but how the central nervous system adapts to this substantial change is poorly understood. In this study, we took advantage of Prestin-/- mice of either sex where prestin, the motor protein in OHCs, was genetically knocked out, therefore removing cochlear amplification completely without changing the cellular structure of the cochlea significantly. While exocytosis from inner hair cells in the cochlea was largely intact, transmission at the endbulb of Held synapse between ANFs and bushy cells in the cochlear nucleus was significantly changed in Prestin-/- mice. Specifically, excitability of bushy cells was significantly increased, due to combination of slightly more depolarized resting membrane potential, increased membrane input resistance, and smaller and briefer afterhyperpolarization. Furthermore, synaptic strength was greatly reduced, caused by substantial decrease in the readily releasable pool (RRP) of synaptic vesicles. Significantly, paired-pulse plasticity at this synapse was reversed from depression in WT mice to facilitation in Prestin-/- mice, likely caused by quicker refilling of RRP observed in Prestin-/- mice. In conclusion, we found that transmission at the endbulb of Held synapse is significantly altered in absence of cochlear amplification, revealing interplay between the peripheral and central processing of auditory signals that contributes to expanded dynamic range of hearing seen in mammals and humans.

  View details for DOI 10.1523/JNEUROSCI.1673-25.2026

  View details for PubMedID 41702721

  View details for PubMedCentralID PMC13022529

• Two-dimensional Ti3C2Tx MXene promotes electrophysiological maturation of neural circuits. Journal of nanobiotechnology Li, Y., Hu, Y., Wei, H., Cao, W., Qi, Y., Zhou, S., Zhang, P., Li, H., Li, G. L., Chai, R. 2022; 20 (1): 398

  Abstract

  The ideal neural interface or scaffold for stem cell therapy shall have good biocompatibility promoting survival, maturation and integration of neural stem cells (NSCs) in targeted brain regions. The unique electrical, hydrophilic and surface-modifiable properties of Ti3C2Tx MXene make it an attractive substrate, but little is known about how it interacts with NSCs during development and maturation.In this study, we cultured NSCs on Ti3C2Tx MXene and examined its effects on morphological and electrophysiological properties of NSC-derived neurons. With a combination of immunostaining and patch-clamp recording, we found that Ti3C2Tx MXene promotes NSCs differentiation and neurite growth, increases voltage-gated current of Ca2+ but not Na+ or K+ in matured neurons, boosts their spiking without changing their passive membrane properties, and enhances synaptic transmission between them.These results expand our understanding of interaction between Ti3C2Tx MXene and NSCs and provide a critical line of evidence for using Ti3C2Tx MXene in neural interface or scaffold in stem cell therapy.

  View details for DOI 10.1186/s12951-022-01590-8

  View details for PubMedID 36045382

  View details for PubMedCentralID PMC9434915

• Generation of mature and functional hair cells by co-expression of Gfi1, Pou4f3, and Atoh1 in the postnatal mouse cochlea. Cell reports Chen, Y., Gu, Y., Li, Y., Li, G. L., Chai, R., Li, W., Li, H. 2021; 35 (3): 109016

  Abstract

  The mammalian cochlea cannot regenerate functional hair cells (HCs) spontaneously. Atoh1 overexpression as well as other strategies are unable to generate functional HCs. Here, we simultaneously upregulated the expression of Gfi1, Pou4f3, and Atoh1 in postnatal cochlear supporting cells (SCs) in vivo, which efficiently converted SCs into HCs. The newly regenerated HCs expressed HC markers Myo7a, Calbindin, Parvalbumin, and Ctbp2 and were innervated by neurites. Importantly, many new HCs expressed the mature and terminal marker Prestin or vesicular glutamate transporter 3 (vGlut3), depending on the subtypes of the source SCs. Finally, our patch-clamp analysis showed that the new HCs in the medial region acquired a large K+ current, fired spikes transiently, and exhibited signature refinement of ribbon synapse functions, in close resemblance to native wild-type inner HCs. We demonstrated that co-upregulating Gfi1, Pou4f3, and Atoh1 enhances the efficiency of HC generation and promotes the functional maturation of new HCs.

  View details for DOI 10.1016/j.celrep.2021.109016

  View details for PubMedID 33882317

• Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells. Neuroscience bulletin Liao, M., Chen, X., Lu, L., Liu, Q., Guo, R., Qiu, Y., Hu, Y., Zhang, Y., Fang, Q., Zhang, P., Li, Y., He, S., Tang, M., Li, H., Li, G. L., Chai, R. 2026; 42 (2): 270-284

  Abstract

  The mammalian cochlea relies on outer and inner hair cells (OHCs/IHCs) for sound amplification and signal transmission. Rab3-interacting molecular binding protein 2 (RIMBP2), expressed in receptor cells and neurons at synaptic active zones, remains poorly characterized in hearing. We therefore generated a Rimbp2 knockout (KO) mouse model (Rimbp2-/-), which exhibited severe hearing loss with elevated thresholds, prolonged latencies, and reduced amplitudes in auditory brainstem response Wave I. OHC loss via apoptosis was correlated with threshold elevation. In IHCs, patch-clamp recordings revealed reduced exocytosis, including a diminished readily-releasable pool, impaired sustained release, and blocked fast endocytosis. Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs. These findings demonstrated RIMBP2's essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.

  View details for DOI 10.1007/s12264-025-01472-7

  View details for PubMedID 40880039

  View details for PubMedCentralID PMC12876471

• Gene editing in a Myo6 semi-dominant mouse model rescues auditory function. Molecular therapy : the journal of the American Society of Gene Therapy Xue, Y., Hu, X., Wang, D., Li, D., Li, Y., Wang, F., Huang, M., Gu, X., Xu, Z., Zhou, J., Wang, J., Chai, R., Shen, J., Chen, Z. Y., Li, G. L., Yang, H., Li, H., Zuo, E., Shu, Y. 2022; 30 (1): 105-118

  Abstract

  Myosin VI（MYO6） is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Y mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Y is 4.05% on average in Myo6WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6WT alleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Y mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

  View details for DOI 10.1016/j.ymthe.2021.06.015

  View details for PubMedID 34174443

  View details for PubMedCentralID PMC8753286

• Deletion of <i>Kcnj16</i> in Mice Does Not Alter Auditory Function FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Lv, J., Fu, X., Li, Y., Hong, G., Li, P., Lin, J., Xun, Y., Fang, L., Weng, W., Yue, R., Li, G., Guan, B., Li, H., Huang, Y., Chai, R. 2021; 9

  View details for DOI 10.3389/fcell.2021.630361

  View details for Web of Science ID 000626059100001