Repeated transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation techniques. In order to investigate the effects of rTMS on the excitability of different types of neurons, this study is conducted to investigate the effects of rTMS on the cognitive function of mice and the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons from the perspective of electrophysiology. In this study, mice were randomly divided into glutaminergic control group, glutaminergic magnetic stimulation group, gamma-aminobutyric acid energy control group, and gamma-aminobutyric acid magnetic stimulation group. The four groups of mice were injected with adeno-associated virus to label two types of neurons and were implanted optical fiber. The stimulation groups received 14 days of stimulation and the control groups received 14 days of pseudo-stimulation. The fluorescence intensity of calcium ions in mice was recorded by optical fiber system. Behavioral experiments were conducted to explore the changes of cognitive function in mice. The patch-clamp system was used to detect the changes of neuronal action potential characteristics. The results showed that rTMS significantly improved the cognitive function of mice, increased the amplitude of calcium fluorescence of glutamergic neurons and gamma-aminobutyric neurons in the hippocampus, and enhanced the action potential related indexes of glutamergic neurons and gamma-aminobutyric neurons. The results suggest that rTMS can improve the cognitive ability of mice by enhancing the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons.
Animals ; Mice ; Hippocampus/cytology* ; Transcranial Magnetic Stimulation ; Neurons/physiology* ; Male ; Cognition/physiology* ; gamma-Aminobutyric Acid/metabolism* ; Action Potentials/physiology*

Brain-computer interface (BCI) technology faces structural risks due to a misalignment between its technological maturity and industrialization expectations. This study used the Technology Readiness Level (TRL) framework to assess the status of major BCI paradigms-such as steady-state visual evoked potential (SSVEP), motor imagery, and P300-and found that they predominantly remained at TRL4 to TRL6, with few stable applications reaching TRL9. The analysis identified four interrelated sources of bubble risk: overly broad definitions of BCI, excessive focus on decoding performance, asynchronous translational progress, and imprecise terminology usage. These distortions have contributed to the misallocation of research resources and public misunderstanding. To foster the sustainable development of BCI, this paper advocated the establishment of a standardized TRL evaluation system, clearer terminological boundaries, stronger support for fundamental research, enhanced ethical oversight, and the implementation of inclusive and diversified governance mechanisms.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual ; Electroencephalography ; Event-Related Potentials, P300

In animal navigation, head direction is encoded by head direction cells within the olfactory-hippocampal structures of the brain. Even in darkness or unfamiliar environments, animals can estimate their head direction by integrating self-motion cues, though this process accumulates errors over time and undermines navigational accuracy. Traditional strategies rely on visual input to correct head direction, but visual scenes combined with self-motion information offer only partially accurate estimates. This study proposed an innovative calibration mechanism that dynamically adjusts the association between visual scenes and head direction based on the historical firing rates of head direction cells, without relying on specific landmarks. It also introduced a method to fine-tune error correction by modulating the strength of self-motion input to control the movement speed of the head direction cell activity bump. Experimental results showed that this approach effectively reduced the accumulation of self-motion-related errors and significantly enhanced the accuracy and robustness of the navigation system. These findings offer a new perspective for biologically inspired robotic navigation systems and underscore the potential of neural mechanisms in enabling efficient and reliable autonomous navigation.
Animals ; Neural Networks, Computer ; Calibration ; Spatial Navigation/physiology* ; Head Movements/physiology* ; Neurons/physiology* ; Models, Neurological ; Head/physiology* ; Action Potentials/physiology*

Objective This study aims to achieve high-yield functional expression of the human voltage-gated potassium channel K_V3.1 using an Escherichia coli cell-free protein synthesis system, thereby providing a novel synthetic approach for drug screening, structural analysis and functional characterization of K_V3.1. Methods K_V3.1 was expressed in an Escherichia coli cell-free protein synthesis system for 10 hours in the presence of peptide surfactant A₆K. The secondary structure of K_V3.1 was analyzed by circular dichroism spectroscopy. The potassium channel activity of the recombinant protein liposome K_V3.1-A₆K was investigated using fluorescent dyes Oxonol VI as indicators, which are capable of reflecting alterations in membrane potential. Results Soluble K_V3.1 protein was successfully synthesized, achieving a purified yield of up to 1.2 mg/mL via an Escherichia coli cell-free protein synthesis system. Circular dichroism spectroscopy revealed that K_V3.1 exhibited characteristic α-helical secondary structures. Membrane potential fluorescence assays demonstrated that the K_V3.1-A₆K proteoliposomes, which were reconstructed with surfactant peptide A₆K, exhibited remarkable potassium ion permeability. Conclusion This study successfully achieved high-yield expression of human K_V3.1 with activity using an Escherichia coli-based cell-free protein synthesis system. This innovative method not only significantly enhances the expression yield of K_V3.1, but also maintains its functional activity, thereby establishing a novel and efficient synthetic platform for drug screening and advancing our understanding of structure-function relationships in K_V3.1 research.
Humans ; Escherichia coli/metabolism* ; Shaw Potassium Channels/biosynthesis* ; Cell-Free System ; Circular Dichroism ; Protein Biosynthesis ; Recombinant Proteins/metabolism* ; Membrane Potentials ; Shab Potassium Channels

Ultrasound has emerged as a non-invasive neural modulation technique. Its mechanisms of action in the brain involve mechanical, cavitation, and thermal effects, which modulate neural activity by activating mechanosensitive ion channels, enhancing cell permeability, and improving blood circulation. The ultrasound-piezo-electric systems, based on the coupling between ultrasound and piezoelectric materials, can generate wireless electrical stimulation to promote neural repair, significantly improving therapeutic outcomes for neurodegenerative diseases and showing potential as a replacement for traditional invasive deep brain stimulation techniques. The ultrasound-responsive piezoelectric drug delivery system combines mechano-electrical conversion capability of piezoelectric materials with the non-invasive penetration advantage of ultrasound. This system achieves synergistic therapeutic effects for neurodegenerative diseases through on-demand drug release and wireless electrical stimulation in deep brain regions. It can effectively overcome the blood-brain barrier limitation, enabling precisely targeted drug delivery to specific brain regions. Simultaneously, it generates electrical stimulation in deep brain areas to exert synergistic neuroreparative effects. Together, these capabilities provide a more precise, efficient, and safe solution for treating neurodegenerative diseases. This review summarizes the neural regulatory mechanisms, technical advantages, and research progress of the ultrasound-responsive piezoelectric drug delivery systems for neurodegenerative disease therapy, aiming to offer novel insights for the field.
Humans ; Neurodegenerative Diseases/drug therapy* ; Drug Delivery Systems/methods* ; Blood-Brain Barrier ; Ultrasonic Waves ; Brain ; Ultrasonic Therapy ; Deep Brain Stimulation/methods*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

Objective:This study aims to investigate the mechanism and potential effects of two exposures to 100 dB sound pressure level（SPL） broadband white noise, with a 14-days interval, on the myelin sheath of the cochlear auditory nerve in mice. The research provides experimental evidence for understanding the pathophysiological processes of noise-induced hearing loss and hidden hearing loss. Methods:Fifteen 6-week-old male C57BL/6J mice with normal hearing thresholds were randomly divided into three groups: a control group（no noise exposure）, a single noise exposure group, and a double noise exposure group. The single noise exposure group was exposed to 100 dB SPL white noise for 2 hours, and ABR thresholds were measured 1 day（P1） and 14 days（P14） after the exposure. The double noise exposure group was exposed to the same conditions of 100 dB SPL white noise for 2 hours, followed by a second identical exposure 14 days later. ABR thresholds were measured 1 day（P15） and 14 days（P28） after the second exposure. The cochleae of all three groups were then collected for immunofluorescence observation of the basilar membrane and transmission electron microscopy to observe changes in the structure of the auditory nerve myelin sheath. Results:In the single noise exposure group, ABR thresholds at all frequencies were significantly elevated compared to the control group at P1. There were no significant changes in ABR thresholds at any frequency at P14. In the double noise exposure group, ABR thresholds at all frequencies were significantly elevated compared to the control group at P15 and P28（P<0.001）. After the first noise exposure, immunofluorescence observation revealed no significant weakening of the auditory nerve myelin sheath signal; transmission electron microscopy showed no significant changes in myelin sheath morphology. However, after the second noise exposure, immunofluorescence observation revealed a weakening of the myelin sheath signal, and transmission electron microscopy showed thinning of the myelin sheath, disruption of the lamellar structure, and separation from the axon, indicating demyelination. Conclusion:Two exposures to 100 dB SPL broadband white noise can lead to damage to the auditory nerve myelin sheath in mice, whereas a single exposure does not cause significant changes.
Animals ; Male ; Myelin Sheath/pathology* ; Mice ; Cochlear Nerve/pathology* ; Mice, Inbred C57BL ; Noise/adverse effects* ; Hearing Loss, Noise-Induced/physiopathology* ; Cochlea ; Evoked Potentials, Auditory, Brain Stem

Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

Objective:To investigate the impact of Waardenburg syndrome（WS） -associated Sox10 p.S100Rfs*9 mutation on inner ear function and its mechanism in noise-induced hearing impairment. Methods:A mice model carrying the Sox10 p.S100Rfs*9 mutation was established using CRISPR-Cas9 gene editing technology. Auditory phenotypes were assessed under baseline conditions and after noise exposure（96 dB SPL, 2 hours）. Auditory brainstem response（ABR） tests were performed to evaluate hearing function, combined with immunofluorescence staining of cochlear basilar membrane whole-mounts to observe hair cells and ribbon synapses. Transcriptome sequencing was conducted to analyze molecular mechanisms. Results:Sox10 p.S100Rfs*9 heterozygous mice exhibited normal hearing thresholds with characteristic ventral pigmentation abnormalities under baseline conditions. Following noise exposure, mutant mice showed significantly higher ABR thresholds at 24 000 Hz compared to wild-type controls（[60.00±6.12]vs[48.13±4.28]dB SPL, P<0.000 1）, and a significant reduction in ribbon synapses（CtBP2-positive puncta） in the basal turn（[55.0±2.3]vs[64.8±3.3]per inner hair cell, P=0.006 6）, while hair cell morphology and number remained intact. Transcriptome analysis revealed altered expression of genes involved in immune regulation, membrane structures, ion channels, and neuroactive ligand-receptor interactions. Conclusion:The Sox10 p.S100Rfs*9 mutation does not alter baseline hearing function but significantly increases inner ear susceptibility to noise damage, primarily manifested as enhanced ribbon synapse vulnerability, especially in high-frequency regions. This gene-environment interaction reveals that Sox10 haploinsufficiency may compromise noise tolerance by affecting synaptic stability and inner ear protective mechanisms. These findings provide new perspectives on the phenotypic heterogeneity in WS patients and theoretical basis for individualized noise protection strategies for patients carrying SOX10 mutations.
Animals ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/physiopathology* ; Mice ; Hearing Loss, Noise-Induced/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Mutation ; Noise ; Disease Models, Animal ; Ear, Inner/physiopathology*