1.Histopathological Insights into Demyelination and Remyelination After Spinal Cord Injury in Non-human Primates.
Junhao LIU ; Zucheng HUANG ; Kinon CHEN ; Rong LI ; Zhiping HUANG ; Junyu LIN ; Hui JIANG ; Jie LIU ; Qingan ZHU
Neuroscience Bulletin 2025;41(8):1429-1447
Demyelination and remyelination play key roles in spinal cord injury (SCI), affecting the recovery of motor and sensory functions. Research in rodent models is extensive, but the study of these processes in non-human primates is limited. Therefore, our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis. In a previous study, we created an SCI model in M. fascicularis by controlling the contusion displacement. We used Eriochrome Cyanine staining, immunohistochemical analysis, and toluidine blue staining to evaluate demyelination and remyelination. The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally, the former mainly impacting sensory pathways, while the latter primarily affected motor pathways. Toluidine blue staining showed myelin loss and axonal distension at the injury site. Schwann cell-derived myelin sheaths were only found at the center, while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas. Our study showed that long-lasting demyelination occurs in the spinal cord of M. fascicularis after SCI, with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
Animals
;
Spinal Cord Injuries/physiopathology*
;
Demyelinating Diseases/etiology*
;
Remyelination/physiology*
;
Macaca fascicularis
;
Disease Models, Animal
;
Myelin Sheath/pathology*
;
Oligodendroglia/pathology*
;
Schwann Cells/pathology*
;
Female
;
Spinal Cord/pathology*
;
Axons/pathology*
2.Evolution of the Rich Club Properties in Mouse, Macaque, and Human Brain Networks: A Study of Functional Integration, Segregation, and Balance.
Xiaoru ZHANG ; Ming SONG ; Wentao JIANG ; Yuheng LU ; Congying CHU ; Wen LI ; Haiyan WANG ; Weiyang SHI ; Yueheng LAN ; Tianzi JIANG
Neuroscience Bulletin 2025;41(9):1630-1644
The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals
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Humans
;
Brain/diagnostic imaging*
;
Mice
;
Male
;
Nerve Net/diagnostic imaging*
;
Macaca
;
Female
;
Neural Pathways/diagnostic imaging*
;
Magnetic Resonance Imaging
;
Biological Evolution
;
Adult
;
Diffusion Magnetic Resonance Imaging
;
Brain Mapping
;
Species Specificity
;
Mice, Inbred C57BL
3.Interactively Integrating Reach and Grasp Information in Macaque Premotor Cortex.
Junjun CHEN ; Guanghao SUN ; Yiwei ZHANG ; Weidong CHEN ; Xiaoxiang ZHENG ; Shaomin ZHANG ; Yaoyao HAO
Neuroscience Bulletin 2025;41(11):1991-2009
Reach-to-grasp movements require integrating information on both object location and grip type, but how these elements are planned and to what extent they interact remains unclear. We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays, requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures. Neural activity in the dorsal premotor cortex (PMd) revealed that reach and grasp were similarly represented yet not independent. Upon receiving the second cue, the PMd continued encoding the first, but over half of the neurons displayed incongruent modulations: enhanced, attenuated, or even reversed. Population-level analysis showed significant changes in encoding structure, forming distinct neural patterns. Leveraging canonical correlation analysis, we identified a shared subspace preserving the initial cue's encoding, contributed by both congruent and incongruent neurons. Together, these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd, providing insights into potential applications for brain-machine interfaces.
Animals
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Motor Cortex/physiology*
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Hand Strength/physiology*
;
Macaca mulatta
;
Psychomotor Performance/physiology*
;
Neurons/physiology*
;
Male
;
Cues
;
Movement/physiology*
;
Gestures
4.A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys.
Yefei CHEN ; Jingyi WANG ; Jing LIU ; Jianbang LIN ; Yunping LIN ; Jinyao NIE ; Qi YUE ; Chunshan DENG ; Xiaofei QI ; Yuantao LI ; Ji DAI ; Zhonghua LU
Neuroscience Bulletin 2024;40(1):90-102
Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals
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Haplorhini
;
Axons
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Motor Neurons
;
Interneurons
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Macaca
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Dependovirus/genetics*
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Genetic Vectors
5.Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque.
Lin YANG ; Min JIN ; Cong ZHANG ; Ning QIAN ; Mingsha ZHANG
Neuroscience Bulletin 2024;40(2):171-181
Even though retinal images of objects change their locations following each eye movement, we perceive a stable and continuous world. One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information. There have been several proposals on how this may be done, including eye-position modulation (gain fields) of retinotopic receptive fields (RFs) and craniotopic RFs. In the present study, we investigated coordinate systems used by RFs in the lateral intraparietal (LIP) cortex and frontal eye fields (FEF) and compared the two areas. We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation. The same recording and analysis procedures were applied to the two brain areas. We found that, in both areas, RFs were distributed from retinotopic to craniotopic representations. There was no significant difference between the distributions in the LIP and FEF. Only a small fraction of neurons was fully craniotopic, whereas most neurons were between the retinotopic and craniotopic representations. The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts. These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF, and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.
Animals
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Macaca
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Visual Fields
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Frontal Lobe/physiology*
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Eye Movements
;
Brain
6.Discovery of a normal-tension glaucoma-suspect rhesus macaque with craniocerebral injury: Hints of elevated translaminar cribrosa pressure difference.
Jian WU ; Qi ZHANG ; Xu JIA ; Yingting ZHU ; Zhidong LI ; Shu TU ; Ling ZHAO ; Yifan DU ; Wei LIU ; Jiaoyan REN ; Liangzhi XU ; Hanxiang YU ; Fagao LUO ; Wenru SU ; Ningli WANG ; Yehong ZHUO
Chinese Medical Journal 2024;137(4):484-486
7.Establishment of a standardized daily behavior collection and analysis system for brain disease models of rhesus and cynomolgus monkeys and its application in autism spectrum disorder.
Xiaofeng REN ; Huimin WANG ; Xiaoman LV ; Yi ZHOU ; Yingyin FAN ; Yanjun YU ; Christoph W TURCK ; Yuhui CHEN ; Longbao LV ; Yingzhou HU ; Hao LI ; Wenchao WANG ; Dongdong QIN ; Xiaoli FENG ; Xintian HU
Journal of Zhejiang University. Science. B 2024;25(11):972-995
Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals
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Autism Spectrum Disorder
;
Macaca mulatta
;
Disease Models, Animal
;
Behavior, Animal
;
Macaca fascicularis
;
Male
;
Humans
8.Neuronal Response to Reward and Luminance in Macaque LIP During Saccadic Choice.
Ziqi WU ; Aihua CHEN ; Xinying CAI
Neuroscience Bulletin 2023;39(1):14-28
Recent work in decision neuroscience suggests that visual saliency can interact with reward-based choice, and the lateral intraparietal cortex (LIP) is implicated in this process. In this study, we recorded from LIP neurons while monkeys performed a two alternative choice task in which the reward and luminance associated with each offer were varied independently. We discovered that the animal's choice was dictated by the reward amount while the luminance had a marginal effect. In the LIP, neuronal activity corresponded well with the animal's choice pattern, in that a majority of reward-modulated neurons encoded the reward amount in the neuron's preferred hemifield with a positive slope. In contrast, compared to their responses to low luminance, an approximately equal proportion of luminance-sensitive neurons responded to high luminance with increased or decreased activity, leading to a much weaker population-level response. Meanwhile, in the non-preferred hemifield, the strength of encoding for reward amount and luminance was positively correlated, suggesting the integration of these two factors in the LIP. Moreover, neurons encoding reward and luminance were homogeneously distributed along the anterior-posterior axis of the LIP. Overall, our study provides further evidence supporting the neural instantiation of a priority map in the LIP in reward-based decisions.
Animals
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Macaca mulatta/physiology*
;
Parietal Lobe
;
Neurons/physiology*
;
Saccades
;
Reward
;
Photic Stimulation
9.Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques.
Dali TONG ; Mei ZHANG ; Yunru YANG ; Han XIA ; Haiyang TONG ; Huajun ZHANG ; Weihong ZENG ; Muziying LIU ; Yan WU ; Huan MA ; Xue HU ; Weiyong LIU ; Yuan CAI ; Yanfeng YAO ; Yichuan YAO ; Kunpeng LIU ; Shifang SHAN ; Yajuan LI ; Ge GAO ; Weiwei GUO ; Yun PENG ; Shaohong CHEN ; Juhong RAO ; Jiaxuan ZHAO ; Juan MIN ; Qingjun ZHU ; Yanmin ZHENG ; Lianxin LIU ; Chao SHAN ; Kai ZHONG ; Zilong QIU ; Tengchuan JIN ; Sandra CHIU ; Zhiming YUAN ; Tian XUE
Protein & Cell 2023;14(1):69-73
10.Electromyographic signals and the starting threshold voltage of orbicularis oris muscle in healthy rhesus monkeys.
Jue Bo YU ; Tian Zhen ZHANG ; Dong Yue XU ; Ke Yong LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(4):368-373
Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.
Animals
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Lip
;
Macaca mulatta
;
Facial Muscles
;
Electromyography

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