Accurately recognizing facial expressions is essential for effective social interactions.Non-human primates(NHPs)are widely used in the study of the neural mechanisms underpinning facial expression processing,yet it r...Accurately recognizing facial expressions is essential for effective social interactions.Non-human primates(NHPs)are widely used in the study of the neural mechanisms underpinning facial expression processing,yet it remains unclear how well monkeys can recognize the facial expressions of other species such as humans.In this study,we systematically investigated how monkeys process the facial expressions of conspecifics and humans using eye-tracking technology and sophisticated behavioral tasks,namely the temporal discrimination task(TDT)and face scan task(FST).We found that monkeys showed prolonged subjective time perception in response to Negative facial expressions in monkeys while showing longer reaction time to Negative facial expressions in humans.Monkey faces also reliably induced divergent pupil contraction in response to different expressions,while human faces and scrambled monkey faces did not.Furthermore,viewing patterns in the FST indicated that monkeys only showed bias toward emotional expressions upon observing monkey faces.Finally,masking the eye region marginally decreased the viewing duration for monkey faces but not for human faces.By probing facial expression processing in monkeys,our study demonstrates that monkeys are more sensitive to the facial expressions of conspecifics than those of humans,thus shedding new light on inter-species communication through facial expressions between NHPs and humans.展开更多
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 retro-gr...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 retro-grade AAV capsids have been shown to offer access to cor-tical 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 retro-grade 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.展开更多
1.The need to develop a holographic digital mannequin Life processes,including high intelligence,self-organization,and homeostasis,are characterized by the biological organism in the form of self-renewal,self-replicat...1.The need to develop a holographic digital mannequin Life processes,including high intelligence,self-organization,and homeostasis,are characterized by the biological organism in the form of self-renewal,self-replication and self-regulation,metabolism,self-repair,and self-reproduction,which are all processes of multisystem coordinated movement[1].Research in the field of life sciences is not limited to the use of advanced observational methods to reveal microscopic structures at the subcellular or molecular level.Discoveries based on these methods alone cannot characterize the dynamic processes of life at the microscopic and molecular level[2].展开更多
On January 29,2024,Elon Musk made a public announcement via social media about the successful implantation of a Neuralink device in humans.Shortly after,a collaborative team from Xuanwu Hospital and Tsinghua Universit...On January 29,2024,Elon Musk made a public announcement via social media about the successful implantation of a Neuralink device in humans.Shortly after,a collaborative team from Xuanwu Hospital and Tsinghua University in China revealed the advancements in their clinical experiment testing the Neural Electronic Opportunity(NEO)—a wireless brain-computer interface(BCI).1 These simultaneous developments sparked widespread interest and renewed enthusiasm for BCIs worldwide.展开更多
The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across ...The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.展开更多
The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial ...The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.展开更多
Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system ...Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system that focuses on rodents.Here,we present MouseVenue3D,an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents.We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module.Then,we validated this process in behavior recognition tasks,and showed that 3-D behavioral data achieved higher accuracy than 2-D data.Subsequently,MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse.Finally,we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice.Our findings reveal that subtle,spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.展开更多
The Ventral Tegmental Area(VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, but little is known about the role of VTA glutamatergic(VGluT2) neurons in these functions.Direct activation o...The Ventral Tegmental Area(VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, but little is known about the role of VTA glutamatergic(VGluT2) neurons in these functions.Direct activation of VGluT2 soma evokes rewarding behaviors, while activation of their downstream projections evokes aversive behaviors. To facilitate our understanding of these conflicting properties, we recorded calcium signals from VTAVGluT2+ neurons using fiber photometry in VGluT2-cre mice to investigate how this population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. To help understand these differences based on VTAVGluT2+ neuronal networks, the inputs and outputs of VTAVGluT2+ neurons were investigated using Cholera Toxin B(CTB) and rabies virus. Based on our results, we propose that the divergent VTAVGluT2+ neuronal responses to aversion and reward conditioning may be partly due to the existence of VTAVGluT2+ subpopulations that are characterized by their connectivity.展开更多
Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the n...Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.展开更多
Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system.It can produce several changes of cognitive behaviors through regulating the release of different neurotr...Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system.It can produce several changes of cognitive behaviors through regulating the release of different neurotransmitters in the brain.However,the effects of nicotine exposure or withdrawal on neurotransmitter metabolism of hippocampus are still unclear.In this study,we real-time evaluated the dynamic alterations in neurotransmitter metabolism of hippocampal neuronal(HT22)cells induced by nicotine exposure and withdrawal at relevant exposure levels of smoking and secondhand smoke by using a microfluidic chip-coupled with liquid chromatography-mass spectrometry(MC-LC-MS)system.We found HT22 cells mainly released related neurotransmitters of tryptophan and choline metabolism,both nicotine exposure and withdraw altered its neurotransmitters and their metabolites release.Exposure to nicotine mainly altered the secretion of serotonin,kynurenic acid,choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition,and the change are closely related to the dose and duration of exposure.Moreover,the altered metabolites could rapidly recover after nicotine withdrawal,but picolinic acid was elevated.MC-LC-MS system used in present study showed a greater advantage to detect unstable metabolites than conventional method by using in vitro model,and the results of dynamic alterations of neurotransmitter metabolism induced by nicotine might provide a potential targets for drug development of neuroprotection or cognitive improvement.展开更多
To survive,animals must process aversive or stressful events quickly,and evaluate and store the related information.Accumulating neural circuity studies have identified key brain nuclei,such as the amygdala,lateral ha...To survive,animals must process aversive or stressful events quickly,and evaluate and store the related information.Accumulating neural circuity studies have identified key brain nuclei,such as the amygdala,lateral habenula (LHb),periaqueductal grey (PAG),ventromedial hypothalamic nucleus,hippocampus,among others,in the processing of negative experiences [1,2].Yet more work is needed to determine how these brain structures coordinate with each other in coping with such experiences.展开更多
Consciousness lies at the heart of our existence and experience.To probe how perceptual consciousness emerges in the brain,we recorded brainwide intracranial electroencephalography signals from human patients while th...Consciousness lies at the heart of our existence and experience.To probe how perceptual consciousness emerges in the brain,we recorded brainwide intracranial electroencephalography signals from human patients while their perceptual consciousness was effectively manipulated using the continuous flash suppression paradigm.We observed substantial differences in brain activities when visual information gradually enters consciousness.展开更多
The ability to detect conspecific's distress is crucial for animal survival.In rodent models,observational fear(OF) occurs when one animal perceives another fear related negative emotions,which may model certain b...The ability to detect conspecific's distress is crucial for animal survival.In rodent models,observational fear(OF) occurs when one animal perceives another fear related negative emotions,which may model certain behaviors caused by witnessing traumatic experiences in humans.Anterior cingulate cortex(ACC) has been showed to play a crucial role in OF.However,cellular and neural circuit basis relating to ACC governing OF is poorly understood.Here,we used Designer Receptor Exclusively Activated by a Designer Drug(DREADD) system to investigate the cell type specific circuit mechanism of ACC in OF.Firstly,inhibitory hM4D(Gi) designer receptor together with clozapine N-oxide(CNO) injection was applied to inactivate ACC neurons in the observer mice.We found that,chemogenetic inhibition of ACC resulted in a decreased freezing response in the observer mice.Next,combining PV-ires-Cre mice and Cre-dependent DREADD system,we selectively targeted the ACC parvalbumin(PV) interneurons with the excitatory hM3D(Gq) designer receptor.Activation of ACC PV interneurons following CNO injection reduced freezing response in the observer mice,while had no effect on freezing response in the demonstrator mice.Finally,monosynaptic rabies retrograde tracing revealed that ACC PV interneurons receive inputs from the mediodorsal thalamic nucleus(MD) and the ventromedial thalamic nucleus(VM),both known for their roles in OF.Taken together,these findings reveal that ACC activation is important for OF,during which PV interneurons in ACC play an important regulatory role.Abnormal function of ACC PV interneurons might contribute to the pathology of empathy-deficits related diseases,such as autism and schizophrenia.展开更多
Key requirements of successful animal behavior research in the laboratory are robustness,objectivity,and high throughput,which apply to both the recording and analysis of behavior.Many automatic methods of monitoring ...Key requirements of successful animal behavior research in the laboratory are robustness,objectivity,and high throughput,which apply to both the recording and analysis of behavior.Many automatic methods of monitoring animal behavior meet these requirements.However,they usually depend on high-performing hardware and sophisticated software,which may be expensive.Here,we describe an automatic infrared behavior-monitor(AIBM)system based on an infrared touchscreen frame.Using this,animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events.This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms.The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient,unbiased,and low-cost manner.展开更多
The lateral habenula(LHb),which is a critical neuroanatomical hub and a regulator of midbrain monoaminergic centers,is activated by events resulting in negative valence and contributes to the expression of both appeti...The lateral habenula(LHb),which is a critical neuroanatomical hub and a regulator of midbrain monoaminergic centers,is activated by events resulting in negative valence and contributes to the expression of both appetitive and aversive behaviors.However,whole-brain cell-type-specific monosynaptic inputs to the LHb in both sexes remain incompletely elucidated.In this study,we used viral tracing combined with in situ hybridization targeting vesicular glutamate transporter 2(vGlut2)and glutamic acid decarboxylase 2(Gad2)to generate a comprehensive whole-brain atlas of inputs to glutamatergic andγ-aminobutyric acid(GABA)ergic neurons in the LHb.We found>30 ipsilateral and contralateral brain regions that projected to the LHb.Of these,there were significantly more monosynaptic LHb-projecting neurons from the lateral septum,anterior hypothalamus,dorsomedial hypothalamus,and ventromedial hypothalamus in females than in males.More interestingly,we found a stronger GABAergic projection from the medial septum to the LHb in males than in females.Our results reveal a comprehensive connectivity atlas of glutamatergic and GABAergic inputs to the LHb in both sexes,which may facilitate a better understanding of sexual dimorphism in physiological and pathological brain functions.展开更多
Dear Editor,Tonic immobility(TI),also termed"feigning death," is the ultimate defensive response to in escapable threats.Since some predators do not like to eat dead animals.
Environmental threats often trigger innate defensive responses in mammals.However,the gradual development of functional properties of these responses during the postnatal development stage remains unclear.Here,we repo...Environmental threats often trigger innate defensive responses in mammals.However,the gradual development of functional properties of these responses during the postnatal development stage remains unclear.Here,we report that looming stimulation in mice evoked fight behavior commencing at P14-16 and had fully developed by P20-24.The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage.Furthermore,the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24.Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and_provide important insight into the underlying mechanism.展开更多
A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of th...A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1(DISC1),and animal models in which this gene has some level of dysfunction show emotion-related impairments.However,it is not known whether DISC1 mouse models have an impairment in avoiding potential risks.In the present study,we used DISC1-N terminal truncation(DISC1-N^(TM))mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze(EPM)and showed reduced social preference in a three-chamber social interaction test.Following EPM tests,c-Fos expression levels indicated that the nucleus accumbens(NAc)was associated with risk-avoidance behavior in DISC1-N^(TM)mice.In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons(FS)in the NAc were significantly lower in DISC1-N^(TM)mice than in wild-type(WT)mice.In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin(PV)neurons in the NAc of DISC1-N^(TM)mice than in WT controls.The impairment of risk avoidance in DISC1-N^(TM)mice was rescued using optogenetic tools that activated NAcPV neurons.Finally,inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N^(TM)mice during tests on the elevated zero maze.Taken together,our findings confirm an impairment in risk avoidance in DISC1-N^(TM)mice and suggest that reduced excitability of NAc^(PV) neurons is responsible.展开更多
On behalf of my colleagues who conducted the study titled"Primate preoptic neurons drive hypothermia and cold defense,"which was recently published in The Innovation,1 I would like to offer a response to Cer...On behalf of my colleagues who conducted the study titled"Primate preoptic neurons drive hypothermia and cold defense,"which was recently published in The Innovation,1 I would like to offer a response to Cerri et al.’s commentary on our study in a correspondence.展开更多
A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal f...A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal for mapping neural circuits. So far, several classes of viral neuronal tracers have become available and provide a powerful toolbox for delineating neural networks. In this paper, we review the recent developments of neurotropic viral tracers and highlight their unique properties in revealing patterns of neuronal connections.展开更多
基金supported by the National Natural Science Foundation of China (U20A2017)Guangdong Basic and Applied Basic Research Foundation (2022A1515010134,2022A1515110598)+2 种基金Youth Innovation Promotion Association of Chinese Academy of Sciences (2017120)Shenzhen-Hong Kong Institute of Brain Science–Shenzhen Fundamental Research Institutions (NYKFKT2019009)Shenzhen Technological Research Center for Primate Translational Medicine (F-2021-Z99-504979)。
文摘Accurately recognizing facial expressions is essential for effective social interactions.Non-human primates(NHPs)are widely used in the study of the neural mechanisms underpinning facial expression processing,yet it remains unclear how well monkeys can recognize the facial expressions of other species such as humans.In this study,we systematically investigated how monkeys process the facial expressions of conspecifics and humans using eye-tracking technology and sophisticated behavioral tasks,namely the temporal discrimination task(TDT)and face scan task(FST).We found that monkeys showed prolonged subjective time perception in response to Negative facial expressions in monkeys while showing longer reaction time to Negative facial expressions in humans.Monkey faces also reliably induced divergent pupil contraction in response to different expressions,while human faces and scrambled monkey faces did not.Furthermore,viewing patterns in the FST indicated that monkeys only showed bias toward emotional expressions upon observing monkey faces.Finally,masking the eye region marginally decreased the viewing duration for monkey faces but not for human faces.By probing facial expression processing in monkeys,our study demonstrates that monkeys are more sensitive to the facial expressions of conspecifics than those of humans,thus shedding new light on inter-species communication through facial expressions between NHPs and humans.
基金supported by Ministry of Science and Technology of China(2019YFA0903803 and 2018YFA0801404)National Natural Science Foundation of China(31871090,32000730,81961128019,and 81901397)+7 种基金Shenzhen Science and Technology Innovation Commission(JCYJ20190809171003698,JCYJ202103243001018,JCYJ20180507182505475,and JCYJ20180504165804015)Shenzhen Technological Research Center for Primate Translational Medicine(F-2021-Z99-504979)Youth Innovation Promotion Association(CAS 2017120)Chinese Academy of Sciences International Partnership Program(172644KYSB20170004)China Postdoctoral Science Foundation(2019M653115.)CAS Key Laboratory of Brain Connectome and Manipulation(2019DP173024)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)International Science and Technology Cooperation Base of Guangdong Province(2019A050505008).
文摘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 retro-grade AAV capsids have been shown to offer access to cor-tical 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 retro-grade 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.
基金supported by the National Natural Science Foundation of China(82293651)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017).
文摘1.The need to develop a holographic digital mannequin Life processes,including high intelligence,self-organization,and homeostasis,are characterized by the biological organism in the form of self-renewal,self-replication and self-regulation,metabolism,self-repair,and self-reproduction,which are all processes of multisystem coordinated movement[1].Research in the field of life sciences is not limited to the use of advanced observational methods to reveal microscopic structures at the subcellular or molecular level.Discoveries based on these methods alone cannot characterize the dynamic processes of life at the microscopic and molecular level[2].
基金National Natural Science Foundation of China(32371066)Guangdong Basic and Applied Basic Research Foundation(2022A1515010134)+1 种基金Shenzhen-Hong Kong Institute of Brain Science–Shenzhen Fundamental Research Institutions(NYKFKT2019009)Shenzhen Technological Research Center for Primate Translational Medicine(F-2021-Z99-504979).
文摘On January 29,2024,Elon Musk made a public announcement via social media about the successful implantation of a Neuralink device in humans.Shortly after,a collaborative team from Xuanwu Hospital and Tsinghua University in China revealed the advancements in their clinical experiment testing the Neural Electronic Opportunity(NEO)—a wireless brain-computer interface(BCI).1 These simultaneous developments sparked widespread interest and renewed enthusiasm for BCIs worldwide.
基金This review was supported by the Key-Area Research and Development Program of Guangdong Province(2018B030331001)the National Natural Science Foundation of China(31630031 and 31930047)+3 种基金the Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence Fund(2019025),the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Chinese Academy of Sciences International Partnership Program(172644KYSB20170004)the CAS President’s International Fellowship for Distinguished Scientists(2021DB0003)the Canadian Institutes of Health Research(#10677).
文摘The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.
基金Supported by the National Natural Science Foundation of China (81420108012,81671046,91832000,and 31700936)the Program of Excellent Talents in Medical Science of Jiangsu Province,China (JCRCA2016006)+4 种基金a Special Project of Clinical Medicine Science and Technology in Jiangsu Province,China (BL2014077)a Guangdong Province Grant (2017A030310496)Key-Area Research and Development Program of Guangdong Province,China (2018B030331001)a National Special Support Grant (W02020453)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017)。
文摘The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.
基金the Key Area R&D Program of Guangdong Province,China(2018B030338001 and 2018B030331001)the National Key R&D Program of China(2018YFA0701403)+11 种基金the National Natural Science Foundation of China(31500861,31630031,91732304,and 31930047)Chang Jiang Scholars Program,the International Big Science Program Cultivating Project of the Chinese Academy of Science(CAS172644KYS820170004)the Strategic Priority Research Program of the CAS(XDB32030100)the Youth Innovation Promotion Association of the CAS(2017413)the CAS Key Laboratory of Brain Connectome and Manipulation(2019DP173024)Shenzhen Government Basic Research Grants(JCYJ20170411140807570,JCYJ20170413164535041)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20160429185235132)a Helmholtz-CAS Joint Research grant(GJHZ1508)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Ten Thousand Talent Program,the Guangdong Special Support Program,Key Laboratory of Shenzhen Institute of Advanced Technology(2019DP173024)the Shenzhen Key Science and Technology Infrastructure Planning Project(ZDKJ20190204002).
文摘Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system that focuses on rodents.Here,we present MouseVenue3D,an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents.We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module.Then,we validated this process in behavior recognition tasks,and showed that 3-D behavioral data achieved higher accuracy than 2-D data.Subsequently,MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse.Finally,we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice.Our findings reveal that subtle,spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.
基金supported by the National Natural Science Foundation of China, China (31630031, 81425010, 31471109, 31671116, and 31500861)International Partnership Program of Chinese Academy of Sciences, China (172644KYS820170004)+7 种基金Helmholtz-CAS Joint Research Grant (GJHZ1508)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, China (2017B030301017)Shenzhen Governmental Grants, China (JCYJ20160429190927063, KQJSCX20160301144002, JCYJ20170413164535041, JCYJ20150 401150223647, JCYJ20160429185854999, JSGG2016042919052 1240)Research Instrument Development Project of the Chinese Academy of Sciences, China (YJKYYQ20170064)Youth Innovation Promotion Association of Chinese Academy of Sciences (2017413)Shenzhen Municipal Funding, China (GJHZ20160229200136090)Shenzhen Discipline Construction Project for Neurobiology, China (DRCSM [2016]1379)Ten Thousand Talent Program, Guangdong Special Support Program, China and Science and Technology Planning Project of Guangdong Province, China (2018B030331001)
文摘The Ventral Tegmental Area(VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, but little is known about the role of VTA glutamatergic(VGluT2) neurons in these functions.Direct activation of VGluT2 soma evokes rewarding behaviors, while activation of their downstream projections evokes aversive behaviors. To facilitate our understanding of these conflicting properties, we recorded calcium signals from VTAVGluT2+ neurons using fiber photometry in VGluT2-cre mice to investigate how this population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. To help understand these differences based on VTAVGluT2+ neuronal networks, the inputs and outputs of VTAVGluT2+ neurons were investigated using Cholera Toxin B(CTB) and rabies virus. Based on our results, we propose that the divergent VTAVGluT2+ neuronal responses to aversion and reward conditioning may be partly due to the existence of VTAVGluT2+ subpopulations that are characterized by their connectivity.
基金supported by the National Natural Science Foundation of China, Nos.31830035, 91732304, 91632303, 81661148053, and 31771156(all to FQX)the Key-Area Research and Development Program of Guangdong Province of China, No.2018B030331001(to FQX)+4 种基金the SIAT Innovation Program for Excellent Young Researchers of China,No.E1G023(to FJ)the Guangdong Basic and Applied Basic Research Foundation of China, No.2021A1515011235(to FQX)Shenzhen Key Laboratory of Viral Vectors for Biomedicine of China, No.ZDSYS20200811142401005(to FQX)the National Basic Research Program(973 Program)of China, No.2015CB755600(to FQX)the Strategic Priority Research Program(B)of China, No.XDB32030200(to FQX)
文摘Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.
基金the National Natural Science Foundation of China(No.22076197)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.YJKYYQ20200034)+2 种基金Shenzhen Engineering Laboratory of Single-molecule Detection and Instrument Development(No.XMHT20190204002)Shenzhen Science and Technology Innovation Commission(No.JCYJ20200109115405930)Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120080)。
文摘Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system.It can produce several changes of cognitive behaviors through regulating the release of different neurotransmitters in the brain.However,the effects of nicotine exposure or withdrawal on neurotransmitter metabolism of hippocampus are still unclear.In this study,we real-time evaluated the dynamic alterations in neurotransmitter metabolism of hippocampal neuronal(HT22)cells induced by nicotine exposure and withdrawal at relevant exposure levels of smoking and secondhand smoke by using a microfluidic chip-coupled with liquid chromatography-mass spectrometry(MC-LC-MS)system.We found HT22 cells mainly released related neurotransmitters of tryptophan and choline metabolism,both nicotine exposure and withdraw altered its neurotransmitters and their metabolites release.Exposure to nicotine mainly altered the secretion of serotonin,kynurenic acid,choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition,and the change are closely related to the dose and duration of exposure.Moreover,the altered metabolites could rapidly recover after nicotine withdrawal,but picolinic acid was elevated.MC-LC-MS system used in present study showed a greater advantage to detect unstable metabolites than conventional method by using in vitro model,and the results of dynamic alterations of neurotransmitter metabolism induced by nicotine might provide a potential targets for drug development of neuroprotection or cognitive improvement.
基金supported by the National Natural Science Foundation of China (31971072 and 81671444)Guangdong International Cooperation Grant (2019A050510032)+1 种基金Shenzhen Science and Technology Innovation Committee Fund(JCYJ20180508152336419)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017)。
文摘To survive,animals must process aversive or stressful events quickly,and evaluate and store the related information.Accumulating neural circuity studies have identified key brain nuclei,such as the amygdala,lateral habenula (LHb),periaqueductal grey (PAG),ventromedial hypothalamic nucleus,hippocampus,among others,in the processing of negative experiences [1,2].Yet more work is needed to determine how these brain structures coordinate with each other in coping with such experiences.
基金This work was supported by the National Natural Science Foundation of China(U20A2017,31830037)the Science and Technology Funds of Guangdong Province(2020A1515111118,2022A1515010134)+2 种基金the Youth Innovation Promotion Association of Chinese Academy of Sciences(2017120)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019009)the Strategic Priority Research Program of Chinese Academy of Sciences(XDBS01030100,XDB32010300),the Ministry of Science and Technology of the People’s Republic of China(2021ZD0203800),and the Fundamental Research Funds for the Central Universities.
文摘Consciousness lies at the heart of our existence and experience.To probe how perceptual consciousness emerges in the brain,we recorded brainwide intracranial electroencephalography signals from human patients while their perceptual consciousness was effectively manipulated using the continuous flash suppression paradigm.We observed substantial differences in brain activities when visual information gradually enters consciousness.
基金partially sponsored by the National Natural Science Foundation of China(NSFC 81425010(L.W.),31630031(L.W.),31500861(Z.Z.),31471109(L.L.)International Partnership Program of Chinese Academy of Sciences,172644KYS820170004(L.W.)+5 种基金External Cooperation Program of the Chinese Academy of Sciences,GJHZ1508(L.W.)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,2017B030301017(L.W.)Shenzhen Governmental Grants,JCYJ20150529143500959(L.W.),JCYJ20150401150223647(Z.Z.),JCYJ20151030140325151(L.L)Shenzhen Governmental grants KQJSCX20160301144002(L.L.)Shenzhen Discipline Construction Project for Neurobiology DRCSM[2016]1379(L.W.)Ten Thousand Talent Program(L.W.)
文摘The ability to detect conspecific's distress is crucial for animal survival.In rodent models,observational fear(OF) occurs when one animal perceives another fear related negative emotions,which may model certain behaviors caused by witnessing traumatic experiences in humans.Anterior cingulate cortex(ACC) has been showed to play a crucial role in OF.However,cellular and neural circuit basis relating to ACC governing OF is poorly understood.Here,we used Designer Receptor Exclusively Activated by a Designer Drug(DREADD) system to investigate the cell type specific circuit mechanism of ACC in OF.Firstly,inhibitory hM4D(Gi) designer receptor together with clozapine N-oxide(CNO) injection was applied to inactivate ACC neurons in the observer mice.We found that,chemogenetic inhibition of ACC resulted in a decreased freezing response in the observer mice.Next,combining PV-ires-Cre mice and Cre-dependent DREADD system,we selectively targeted the ACC parvalbumin(PV) interneurons with the excitatory hM3D(Gq) designer receptor.Activation of ACC PV interneurons following CNO injection reduced freezing response in the observer mice,while had no effect on freezing response in the demonstrator mice.Finally,monosynaptic rabies retrograde tracing revealed that ACC PV interneurons receive inputs from the mediodorsal thalamic nucleus(MD) and the ventromedial thalamic nucleus(VM),both known for their roles in OF.Taken together,these findings reveal that ACC activation is important for OF,during which PV interneurons in ACC play an important regulatory role.Abnormal function of ACC PV interneurons might contribute to the pathology of empathy-deficits related diseases,such as autism and schizophrenia.
基金This work was supported by a Shenzhen Governmental Grant(JCYJ20180302145710934)the National Natural Science Foundation of China(31700907 and 31700908)+6 种基金the Key-Area Research and Development Program of Guangdong Province(2018B030331001)the International Partnership Program of the Chinese Academy of Sciences(172644KYS820170004)the Strategic Priority Research Program of Chinese Academy of Science(XDB32030100)Guangdong Special Support Program([2018]9)Ten Thousand Talent ProgramKey Laboratory of SIAT(2019DP173024)the Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences.
文摘Key requirements of successful animal behavior research in the laboratory are robustness,objectivity,and high throughput,which apply to both the recording and analysis of behavior.Many automatic methods of monitoring animal behavior meet these requirements.However,they usually depend on high-performing hardware and sophisticated software,which may be expensive.Here,we describe an automatic infrared behavior-monitor(AIBM)system based on an infrared touchscreen frame.Using this,animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events.This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms.The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient,unbiased,and low-cost manner.
基金This work was supported by the NSFC-Guangdong Joint Fund(U20A6005)the National Natural Science Foundation of China(31630031 and 31930047)+2 种基金the Key-Area Research and Development Program of Guangdong Province(2018B030340001 and 2018B030331001)the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Shenzhen Key Laboratory of Translational Research for Brain Diseases(ZDSYS20200828154800001).
文摘The lateral habenula(LHb),which is a critical neuroanatomical hub and a regulator of midbrain monoaminergic centers,is activated by events resulting in negative valence and contributes to the expression of both appetitive and aversive behaviors.However,whole-brain cell-type-specific monosynaptic inputs to the LHb in both sexes remain incompletely elucidated.In this study,we used viral tracing combined with in situ hybridization targeting vesicular glutamate transporter 2(vGlut2)and glutamic acid decarboxylase 2(Gad2)to generate a comprehensive whole-brain atlas of inputs to glutamatergic andγ-aminobutyric acid(GABA)ergic neurons in the LHb.We found>30 ipsilateral and contralateral brain regions that projected to the LHb.Of these,there were significantly more monosynaptic LHb-projecting neurons from the lateral septum,anterior hypothalamus,dorsomedial hypothalamus,and ventromedial hypothalamus in females than in males.More interestingly,we found a stronger GABAergic projection from the medial septum to the LHb in males than in females.Our results reveal a comprehensive connectivity atlas of glutamatergic and GABAergic inputs to the LHb in both sexes,which may facilitate a better understanding of sexual dimorphism in physiological and pathological brain functions.
基金This work was supported in part by the Key-Area Research and Development Program of Guangdong Province(2018B030331001 and 2018B030338001)the National Natural Science Foundation of China(31600860,31630031,31930047,and 91732304)+7 种基金the International Partnership Program of the Chinese Academy of Sciences(172644KYS820170004)the Key Laboratory of the CAS(2019DP173024)the Strategic Priority Research Program of Chinese Academy of Science(XDB32030100)the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Ten Thousand Talent Program,the Chang Jiang Scholars Program,the Guangdong Special Support Program,the Guangdong Provincial Natural Science Foundation(2018A030313439)the Helmholtz-CAS joint research grant(GJHZ1508)the Shenzhen Government Basic Research Grants(JCYJ20170413164535041)the Shenzhen Key Science and Technology Infrastructure Planning Project(ZDKJ20190204002)。
文摘Dear Editor,Tonic immobility(TI),also termed"feigning death," is the ultimate defensive response to in escapable threats.Since some predators do not like to eat dead animals.
基金This work was supported by the National Natural Science Foundation of China(31930047,91732304 and 31630031)The Strategic Priority Research Program of the Chinese Academy of Science(XDB32030100)+9 种基金Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Natural,Science Foundationo Gfuangdong,Province(2018A030313439)a Shenzhen Government grant(JCYJ20170413164535041)Shenzhen Key Science and Technology Infrastructure Planning Project(ZDKJ20190204002)Key Laboratory of CAS(2019DP173024)The Ten Thousand Talents ProgramThe Guangdong Special Support ProgramChang Jiang Scholars ProgramIntermational PartnershipProgram of theChinese Academy of Sciences(172644KYS820170004)and the Key-Area Research and Development Program of Guangdong Province(2018B030331001).
文摘Environmental threats often trigger innate defensive responses in mammals.However,the gradual development of functional properties of these responses during the postnatal development stage remains unclear.Here,we report that looming stimulation in mice evoked fight behavior commencing at P14-16 and had fully developed by P20-24.The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage.Furthermore,the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24.Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and_provide important insight into the underlying mechanism.
基金This work was supported by the National Natural Science Foundation of China(31671116,31761163005,31800881,and 91132306)the International Big Science Program Cultivation Project of Chinese Academy of Sciences(172644KYS820170004)+3 种基金the External Cooperation Program of the Chinese Academy of Sciences(172644KYSB20160057)Science and Technology Program of Guangzhou Municipality(202007030001)the Key-Area Research and Development Program of Guangdong Province(2018B030331001 and 2018B03033600)Shenzhen Government Basic Research Grants(JCYJ20200109115405930 and JCYJ20200109150717745).
文摘A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1(DISC1),and animal models in which this gene has some level of dysfunction show emotion-related impairments.However,it is not known whether DISC1 mouse models have an impairment in avoiding potential risks.In the present study,we used DISC1-N terminal truncation(DISC1-N^(TM))mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze(EPM)and showed reduced social preference in a three-chamber social interaction test.Following EPM tests,c-Fos expression levels indicated that the nucleus accumbens(NAc)was associated with risk-avoidance behavior in DISC1-N^(TM)mice.In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons(FS)in the NAc were significantly lower in DISC1-N^(TM)mice than in wild-type(WT)mice.In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin(PV)neurons in the NAc of DISC1-N^(TM)mice than in WT controls.The impairment of risk avoidance in DISC1-N^(TM)mice was rescued using optogenetic tools that activated NAcPV neurons.Finally,inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N^(TM)mice during tests on the elevated zero maze.Taken together,our findings confirm an impairment in risk avoidance in DISC1-N^(TM)mice and suggest that reduced excitability of NAc^(PV) neurons is responsible.
文摘On behalf of my colleagues who conducted the study titled"Primate preoptic neurons drive hypothermia and cold defense,"which was recently published in The Innovation,1 I would like to offer a response to Cerri et al.’s commentary on our study in a correspondence.
基金supported by the National Natural Science Foundation of China (31671119 and 31871090)the Shenzhen Science and Technology Innovation Commission (JCYJ20160428164440255, JCYJ20170413162938668, JCYJ20170818155056369, and JCYJ20170307170742519)+3 种基金the Shenzhen Discipline Construction Project for Neurobiology (DRCSM [2016]1379)the Japan Society for the Promotion of Science KAKENHI (JP18K08494) the Japan Science and Technology Agency PRESTO (JPMJPR1784)the Ono Medical Research Foundation, and the Novartis Foundation (Japan) for the Promotion of Science
文摘A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal for mapping neural circuits. So far, several classes of viral neuronal tracers have become available and provide a powerful toolbox for delineating neural networks. In this paper, we review the recent developments of neurotropic viral tracers and highlight their unique properties in revealing patterns of neuronal connections.
