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Rapid Unconscious Acquisition of Conditioned Fear with Low-Spatial-Frequency but Emotionally Neutral Stimuli

Research 2024年第1期2023卷 753-762页

作者： Yujie Chen Si Chen Zhongju Sun Xilei Zhang Xiangyong Yuan Liang Wang Yi Jiang State Key Laboratory of brain and cognitive sciences CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China Chinese Institute for brain Research Beijing 102206China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China

It has long been proposed that emotionally“prepared”(i.e.,fear-related)stimuli are privileged in the unconscious acquisition of conditioned fear.However,as fear processing is suggested to highly depend on the coarse,low-spatial-frequency(LSF)components of the fear-related stimuli,it is plausible that LSF may play a unique role in the unconscious fear conditioning even with emotionally neutral stimuli.Here,we provided empirical evidence that,following classical fear conditioning,an invisible,emotionally neutral conditioned stimulus(CS+)with LSF,but not with high spatial frequency(HSF),can rapidly elicit stronger skin conductance responses(SCRs)and larger pupil diameters than its CS−counterpart.In comparison,consciously perceived emotionally neutral CS+with LSF and HSF elicited comparable SCRs.Taken together,these results support that the unconscious fear conditioning does not necessarily entail emotionally prepared stimuli but prioritizes LSF information processing and highlight the crucial distinctions between the unconscious and the conscious fear learning.These findings not only coincide with the postulation that a rapid,spatial-frequency-dependent subcortical route is engaged in unconscious fear processing but also suggest the existence of multiple routes for conscious fear processing.

关键词： neutral necessarily diameters

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Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

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Neural Regeneration Research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun Guangxi Key Laboratory of brain and cognitive Neuroscience Guilin Medical University department of Genetic Disease Research Osaka Metropolitan University Graduate School of Medicine department of Scientific Research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

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Local field potentials,spiking activity,and receptive fields in human visual cortex

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Science China(Life sciences) 2024年第3期67卷 543-554页

作者： Lu Luo Xiongfei Wang Junshi Lu Guanpeng Chen Guoming Luan Wu Li Qian Wang Fang Fang School of Psychological and cognitive sciences and Beijing Key Laboratory of Behavior and Mental Health Peking UniversityBeijing 100871China School of Psychology Beijing Sport UniversityBeijing 100084China department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China Beijing Key Laboratory of Epilepsy Epilepsy CenterSanbo Brain HospitalCapital Medical UniversityBeijing 100093China IDG/McGovern Institute for brain Research Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life sciences Peking UniversityBeijing 100871China Beijing Institute for brain Disorders Beijing 100069China State Key Laboratory of cognitive Neuroscience and Learning and IDG/McGovern Institute for brain Research Beijing Normal UniversityBeijing 100875China

The concept of receptive field(RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals,while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials(LFPs) and spiking activity in human visual cortex(V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from lowfrequency activity(LFA, 0.5–30 Hz) were larger than those estimated from low-gamma activity(LGA, 30–60 Hz) and high-gamma activity(HGA, 60–150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.

关键词： human visual cortex receptive field intracranial EEG local field potential spiking activity

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Temporal Unfolding of Racial Ingroup Bias in Neural Responses to Perceived Dynamic Pain in Others

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Neuroscience Bulletin 2024年第2期40卷 157-170页

作者： Chenyu Pang Yuqing Zhou Shihui Han School of Psychological and cognitive sciences PKU-IDG/McGovern Institute for Brain ResearchBeijing Key Laboratory of Behavior and Mental HealthPeking UniversityBeijing 100081China CAS Key Laboratory of Behavioral Science Institute of PsychologyChinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China

In this study,we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions.We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful(or non-painful)stimulation to Asian and White models’faces to trigger painful(or neutral)expressions.We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms–200 ms,in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms–200 ms,in the anterior cingulate cortex around 250 ms–350 ms,and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset.Perceived dynamic pain in White models modulated activities in the visual,anterior cingulate,and primary sensory cortices after 500 ms.Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race(vs other-race)individuals in dynamic painful situations.

关键词： Empathy Race Magnetoencephalography Dynamic pain Cingulate cortex

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How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University department of Computer sciences Tsinghua University College of Life sciences Nankai University Chinese Institute for brain Research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

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brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key Laboratory of cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science Laboratory National Institute of Biological sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+neurons.These Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

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Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

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Neural Regeneration Research 2024年第5期19卷 1133-1141页

作者： Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghaiChina Shanghai Key Laboratory of brain Functional Genomics(Ministry of Education) Affiliated Mental Health Center(ECNU)School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina Shanghai Changning Mental Health Center ShanghaiChina NYU-ECNU Institute of brain and cognitive Science at NYU Shanghai ShanghaiChina Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai ShanghaiChina

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

关键词： behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current mRNA-Seq

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Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1241-1248页

作者： Tingting Han Yuxiang Xu Lin Sun Makoto Hashimoto Jianshe Wei Institute for brain sciences Research School of Life Sciences Henan University College of Chemistry and Molecular sciences Henan University department of Basic Technology Tokyo Metropolitan Institute of Medical Science

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging; they have a great impact on the aging process and are the main risk factors for neurodegeneration. Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases. This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s chorea, and Parkinson’s disease. This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states. Therefore, inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

关键词： aging Alzheimer’s disease cytokines Huntington’s disease microglia neurodegenerative diseases neuroinflammation neuroprotection neurotoxicity Parkinson’s disease

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Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National Science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of Life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of Life sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences department of Modern Life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice.Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

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Photonic neuromorphic architecture for tens-of-task lifelong learning

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Light(Science & Applications) 2024年第3期13卷 519-530页

作者： Yuan Cheng Jianing Zhang Tiankuang Zhou Yuyan Wang Zhihao Xu Xiaoyun Yuan Lu Fang Sigma Laboratory Department of Electronic EngineeringTsinghua UniversityBeijing 100084China Beijing National Research Center for Information Science and Technology(BNRist) Beijing 100084China Institute for brain and cognitive Science Tsinghua University(THUIBCS)Beijing 100084China

Scalable,high-capacity,and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks.Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls,hindering them from the sustainable performance improvement and iterative multi-task learning.Referring to another modality of light,photonic computing has been progressively applied in high-efficient neuromorphic systems.Here,we innovate a reconfigurable lifelong-learning optical neural network(L2 ONN),for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware codesign.Benefiting from the inherent sparsity and parallelism in massive photonic connections,L2 ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field,while incrementally acquiring expertise on various tasks by gradually enlarging the activation.The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths.Extensive evaluations on freespace and on-chip architectures confirm that for the first time,L2 ONN avoided the catastrophic forgetting issue of photonic computing,owning versatile skills on challenging tens-of-tasks(vision classification,voice recognition,medical diagnosis,etc.)with a single model.Particularly,L2 ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks,and 14×larger capacity than existing optical neural networks while maintaining competitive performance on each individual task.The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme,permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

关键词： life neural versatile

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