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Development and transdifferentiation into inner hair cells require Tbx2

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National science Review 2022年第12期9卷 135-148页

作者： Zhenghong Bi Xiang Li Minhui Ren Yunpeng Gu Tong Zhu Shuting Li Guangqin Wang Suhong Sun Yuwei Sun Zhiyong Liu Institute of Neuroscience State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences University of Chinese Academy of sciences Shanghai center for brain science and brain-Inspired Intelligence technology

Atohl is essential for the development of both outer hair cells(OHCs) and inner hair cells(IHCs) in the mammalian co chlea.Whereas Ikzf2 is necessary for OHC development,the key gene re quired for IHC development remains unknown.We found that deletion of Tbx2 in neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% of IHC genes and inducing 56.3% of OHC genes,including Ikzf2.More importantly,persistent expression of Tbx2 coupled with transient Atohl expression effe ctively reprogrammed non-sensory supporting cells into new IHCs expressing the functional IHC marker vGlut3.The differentiation status of these new IHCs was considerably more advanced than that previously reported.Thus,Tbx2 is essential for IHC development and co-upregulation of Tbx2 with Atohl in supporting cells represents a new approach for treating deafness related to IHC degeneration.

关键词： Tbx2 cochlea inner hair cell supporting cell Ikzf2 outer hair cell

Cloning of a gene-edited macaque monkey by somatic cell nuclear transfer

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National science Review 2019年第1期6卷 101-108页

作者： Zhen Liu Yijun Cai Zhaodi Liao Yuting Xu Yan Wang Zhanyang Wang Xiaoyu Jiang Yuzhuo Li Yong Lu Yanhong Nie Xiaotong Zhang Chunyang Li Xinyan Bian Mu-ming Poo Hung-Chun Chang Qiang Sun Institute of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology CAS Key Laboratory of Primate Neurobiology State Key Laboratory of Neuroscience Chinese Academy of Sciences Shanghai research center for brain science and brain-inspired technology

Cloning of macaque monkeys by somatic cell nucleus transfer(SCNT) allows the generation of monkeys with uniform genetic backgrounds that are useful for the development of non-human primate models of human diseases. Here, we report the feasibility of this approach by SCNT of fibroblasts from a macaque monkey(Macaca fascicularis), in which a core circadian transcription factor BMAL1 was knocked out by clustered regularly interspaced short palindromic repeat/Cas9 gene editing(see accompanying paper).Out of 325 SCNT embryos transferred into 65 surrogate monkeys, we cloned five macaque monkeys with BMAL1 mutations in both alleles without mosaicism, with nuclear genes identical to that of the fibroblast donor monkey. Further peripheral blood m RNA analysis confirmed the complete absence of the wild-type BMAL1 transcript. This study demonstrates that the SCNT approach could be used to generate cloned monkeys from fibroblasts of a young adult monkeys and paves the way for the development of macaque monkey disease models with uniform genetic backgrounds.

关键词： macaque monkey cloning somatic cell nuclear transfer non-human primate models CRISPR/Cas9 gene editing circadian rhythm disorders

Accelerated passage of gene-modified monkeys by hormone-induced precocious puberty

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National science Review 2021年第7期8卷 68-71页

作者： Zhen Liu Kui Li Yijun Cai Qiming Liu Tikui Zhang Yong Lu Yanhong Nie Yan Wang Zhiguang Yan Yinwei Qu Yuzhuo Li Zhanyang Wang Zhi-Qi Xiong Qiang Sun Institute of Neuroscience State Key Laboratory of Neuroscience CAS Key Laboratory of Primate Neurobiology CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai Research Center for Brain Science and Brain-Inspired Intelligence

Mosaicism occurs in most founder genemodified monkeys generated by virus infection and programmable-nucleases[1–3]. In addition, macaque monkeys have a long preadolescence period, with four or more years usually required for male macaque monkeys to become sexually mature [4,5]. The mosaicism and long time to sexual maturity have largely prevented wide usage of gene-modified monkey models.

关键词： non-human primates gene editing passage acceleration precocious puberty

Prompt learning in computer vision: a survey

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Frontiers of Information technology & Electronic Engineering 2024年第1期25卷 42-63页

作者： Yiming LEI Jingqi LI Zilong LI Yuan CAO Hongming SHAN Shanghai Key Laboratory of Intelligent Information Processing School of Computer ScienceFudan UniversityShanghai 200438China Institute of science and technology for brain-Inspired Intelligence Fudan UniversityShanghai 200433China MOE Frontiers center for brain science Fudan UniversityShanghai 200433China Shanghai center for brain science and brain-Inspired technology Shanghai 201210China

Prompt learning has attracted broad attention in computer vision since the large pre-trained visionlanguagemodels (VLMs) exploded. Based on the close relationship between vision and language information builtby VLM, prompt learning becomes a crucial technique in many important applications such as artificial intelligencegenerated content (AIGC). In this survey, we provide a progressive and comprehensive review of visual promptlearning as related to AIGC. We begin by introducing VLM, the foundation of visual prompt learning. Then, wereview the vision prompt learning methods and prompt-guided generative models, and discuss how to improve theefficiency of adapting AIGC models to specific downstream tasks. Finally, we provide some promising researchdirections concerning prompt learning.

关键词： Prompt learning Visual prompt tuning(VPT) Image generation Image classification Artificial intelligence generated content(AIGC)

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An interview with Mingjie Zhang: phase separation in biological systems

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National science Review 2021年第9期8卷 192-195页

作者： Weijie Zhao Mu-ming Poo NSR the CAS center for Excellence in brain science and Intelligence technology

Mingjie Zhang is a distinguished structural biologist whose research interest is the protein assemblies in cells, particularly those at the synapse, where two neurons meet and transmit nervous impulses from one to the other. In recent years, his group discovered the phenomenon of phase separation in both the pre-and post-synaptic sites of neurons and elucidated its regulation and physiological function. In this interview, NSR Executive Editor-in-Chief Mu-ming Poo talks with Prof. Zhang on the fast-developing research area of biological phase separation, as well as Zhang’s new role as the Founding Dean of the School of Life sciences at Southern University of science and technology(SUSTech) in Shenzhen.

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An Easily Compatible Eye-tracking System for Freely-moving Small Animals

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Neuroscience Bulletin 2022年第6期38卷 661-676页

作者： Kang Huang Qin Yang Yaning Han Yulin Zhang Zhiyi Wang Liping Wang Pengfei Wei Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation center for brain science Guang-dong Provincial Key Laboratory of Brain Connectome and BehaviorCAS Center for Excellence in Brain Science and Intelligence TechnologyBrain Cognition and Brain Disease InstituteShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Seiences Bejing 100049China Harbin Institute of technology Shenzhen Shenzhen 518055.China

Measuring eye movement is a fundamental approach in cognitive science as it provides a variety of insightful parameters that reflect brain states such as visual attention and emotions.Combining eye-tracking with multimodal neural recordings or manipulation techniques is beneficial for understanding the neural substrates of cognitive function.Many commercially-available and custom-built systems have been widely applied to awake,head-fixed small animals.However,the existing eyetracking systems used in freely-moving animals are still limited in terms of their compatibility with other devices and of the algorithm used to detect eye movements.Here,we report a novel system that integrates a general-purpose,easily compatible eye-tracking hardware with a robust eye feature-detection algorithm.With ultra-light hardware and a detachable design,the system allows for more implants to be added to the animal's exposed head and has a precise synchronization module to coordinate with other neural implants.Moreover,we systematically compared the performance of existing commonly-used pupil-detection approaches,and demonstrated that the proposed adaptive pupil feature-detection algorithm allows the analysis of more complex and dynamic eye-tracking data in freemoving animals.Synchronized eye-tracking and electroencephalogram recordings,as well as algorithm validation under five noise conditions,suggested that our system is flexibly adaptable and can be combined with a wide range of neural manipulation and recording technologies.

关键词： Eye-tracking Freely-moving Head-mounted device Pupil detection Adaptive Kalman filter

Neural Integration of Audiovisual Sensory Inputs in Macaque Amygdala and Adjacent Regions

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Neuroscience Bulletin 2023年第12期39卷 1749-1761页

作者： Liang Shan Liu Yuan Bo Zhang Jian Ma Xiao Xu Fei Gu Yi Jiang Ji Dai CAS Key Laboratory of brain Connectome and Manipulation the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Shenzhen-Hong Kong Institute of brain science-Shenzhen Fundamental research Institutions Shenzhen 518055China University of Chinese Academy of sciences Beijing 100049China State Key Laboratory of brain and Cognitive science CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China Chinese Institute for brain research Beijing 102206China Shenzhen Technological research center for Primate Translational Medicine Shenzhen 518055China Key Laboratory of brain science Zunyi Medical UniversityZunyi563000China

Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain.Subcortical regions such as the amygdala are involved in sensory processing including vision and audition,yet their roles in multisensory integration remain unclear.In this study,we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual stimuli.From a sample of 332 neurons,we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation,which could be classified into four types with differentiated regional origins.Using the hierarchical clustering method,neurons were further clustered into five groups and associated with different integrating functions and sub-regions.Finally,regions distinguishing congruent and incongruent bimodal sensory inputs were identified.Overall,visual processing dominates audiovisual integration in the amygdala and adjacent regions.Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain.

关键词： Macaque Amygdala-Multisensory Audiovisual integration Neural activity Multichannel recording

Influence of Recent Trial History on Interval Timing

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Neuroscience Bulletin 2023年第4期39卷 559-575页

作者： Taorong Xie Can Huang Yijie Zhang Jing Liu Haishan Yao Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of sciences Beijing 100049China Shanghai center for brain science and brain-Inspired Intelligence technology Shanghai 201210China

Interval timing is involved in a variety of cognitive behaviors such as associative learning and decision-making.While it has been shown that time estimation is adaptive to the temporal context,it remains unclear how interval timing behavior is influenced by recent trial history.Here we found that,in mice trained to perform a licking-based interval timing task,a decrease of inter-reinforcement interval in the previous trial rapidly shifted the time of anticipatory licking earlier.Optogenetic inactivation of the anterior lateral motor cortex(ALM),but not the medial prefrontal cortex,for a short time before reward delivery caused a decrease in the peak time of anticipatory licking in the next trial.Electrophysiological recordings from the ALM showed that the response profiles preceded by short and long inter-reinforcement intervals exhibited task-engagement-dependent temporal scaling.Thus,interval timing is adaptive to recent experience of the temporal interval,and ALM activity during time estimation reflects recent experience of interval.

关键词： Peak-interval timing procedure Temporal context Trial history Secondary motor cortex Temporal scaling

The Secondary Motor Cortex-striatum Circuit Contributes to Suppressing Inappropriate Responses in Perceptual Decision Behavior

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Neuroscience Bulletin 2023年第10期39卷 1544-1560页

作者： Jing Liu Dechen Liu Xiaotian Pu Kexin Zou Taorong Xie Yaping Li Haishan Yao Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of sciences Beijing 100049China Shanghai center for brain science and brain-Inspired Intelligence technology Shanghai 201210China

The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear.Using mice performing a visual Go/No-Go task,we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm(FA)rate to the reward-irrelevant No-Go stimulus.The choice signal of M2 neurons correlated with behavioral performance,and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS.By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs,we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus,and inactivating their early responses increased the FA rate.These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.

关键词： Secondary motor cortex Striatum Visual perceptual decision Choice signal Direct and indirect pathway striatal neurons