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
Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of sufferin...Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.展开更多
The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted...The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted to specific organs or tissues.Investigating whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is essential.In this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila melanogaster.Results indicated that the particles caused gut damage and remained within the digestive system.Continuous MP exposure significantly shortened the lifespan of adult flies.Even short-term exposure disrupted sleep patterns,increasing the length of daytime sleep episodes.Additionally,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated females.Although MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these tissues.In the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related pathways.In the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism.Overall,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.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
Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(S...Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.展开更多
The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire b...Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.展开更多
Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the ne...Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the neurophysiological properties of single neuron is still unclear.To tackle this issue,different shape GNPs(nanosphere,nanotriakisoctahedron and nanoflower)were synthesized to investigate the effect of GNPs on the voltage-dependent sodium channel and the action potential(AP)of hippocampal CA1 neurons in mice.The results indicated that GNPs inhibited the amplitudes of voltage-gated sodium current(I_(Na))and led to a hyperpolarizing shift in the voltage-dependence curve of both activation and inactivation of I_(Na).GNPs also increased neuronal excitability and altered some properties of AP.Moreover,most alterations in AP properties were observed in nanoflower GNPs treated CA1 neurons,suggesting that the neurotoxicity of gold nanoparticles is surface roughness-dependent.These results may provide a valuable direction in the clinical application of GNPs.展开更多
The kidneys are essential organs that help maintain homeostasis,and their function is regulated by the neural system.Despite the anatomical multi-synaptic connection between the central autonomic nuclei and the kidney...The kidneys are essential organs that help maintain homeostasis,and their function is regulated by the neural system.Despite the anatomical multi-synaptic connection between the central autonomic nuclei and the kidneys,it remains unclear whether there are any variations in neural connections between the nervous systems and the renal cortex and medulla in male and female mice.Here,we used the pseudorabies virus to map the central innervation network of the renal cortex and medulla in both sexes.The data revealed that specific brain regions displayed either a contralateral-bias or ipsilateral-bias pattern while kidney-innervating neurons distributed symmetrically in the midbrain and hindbrain.Sex differences were observed in the distribution of neurons connected to the left kidney,as well as those connected to the renal cortex and medulla.Our findings provide a comprehensive understanding of the brain-kidney network in both males and females and may help shed light on gender differences in kidney function and disease susceptibility in humans.展开更多
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 includin...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.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
Dear Editor,Alzheimer's disease(AD)is one of the most devastating neurodegenerative disorders and the most common form of dementia.Synaptic loss is a hallmark of AD pathology and exacerbates cognitive impairment[1...Dear Editor,Alzheimer's disease(AD)is one of the most devastating neurodegenerative disorders and the most common form of dementia.Synaptic loss is a hallmark of AD pathology and exacerbates cognitive impairment[1].Synaptic loss,unlike neuronal loss,is reversible due to the highly dynamic properties of synapses.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
The use of animals in research has long been debated.In particular,the use of nonhuman primates(NHPs)in either basic or applied research is controversial[1,2].The concerns mainly arise from an ethical perspective give...The use of animals in research has long been debated.In particular,the use of nonhuman primates(NHPs)in either basic or applied research is controversial[1,2].The concerns mainly arise from an ethical perspective given the great similarity between NHPs and humans.While this similarity has scientific advantages,it has also raised concerns that experimental primates may experience pain and suffering in ways similar to humans.展开更多
The biological basis of consciousness is one of the hardest questions in Science[1].To understand how consciousness arises from physical components,the brain has been studied systematically for decades.Damage to some ...The biological basis of consciousness is one of the hardest questions in Science[1].To understand how consciousness arises from physical components,the brain has been studied systematically for decades.Damage to some structures of the brainstem leads to temporary or persistent loss of consciousness,yet damage to other parts of the brain may lead to limited deficits in certain aspects of awareness.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
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
During free exploration,the emergence of patterned and sequential behavioral responses to an unknown environment reflects exploration traits and adaptation.However,the behavioral dynamics and neural substrates underly...During free exploration,the emergence of patterned and sequential behavioral responses to an unknown environment reflects exploration traits and adaptation.However,the behavioral dynamics and neural substrates underlying the exploratory behavior remain poorly understood.We developed computational tools to quantify the exploratory behavior and performed in vivo electrophysiological recordings in a large arena in which mice made sequential excursions into unknown territory.Occupancy entropy was calculated to characterize the cumulative and moment-to-moment behavioral dynamics in explored and unexplored territories.Local field potential analysis revealed that the theta activity in the dorsal hippocampus(d HPC)was highly correlated with the occupancy entropy.Individual d HPC and prefrontal cortex(PFC)oscillatory activities could classify various aspects of free exploration.Initiation of exploration was accompanied by a coordinated decrease and increase in theta activity in PFC and d HPC,respectively.Our results indicate that d HPC and PFC work synergistically in shaping free exploration by modulating exploratory traits during emergence and visits to an unknown environment.展开更多
Dear Editor,The subthalamic nucleus(STN)is a major component of the evolutionarily-conserved basal ganglia structures[1].While the beneficial effects of deep brain stimulation(DBS)of the STN on motor symptoms in patie...Dear Editor,The subthalamic nucleus(STN)is a major component of the evolutionarily-conserved basal ganglia structures[1].While the beneficial effects of deep brain stimulation(DBS)of the STN on motor symptoms in patients with Parkinson's disease(PD)are indisputable,several non-motor symptoms can arise following DBS,including elevated depression and perception of fear in addition to altered sleep-wake parameters.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 the Shenzhen Key Laboratory of Drug Addiction (ZDSYS20190902093601675)CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024)+2 种基金National Natural Science Foundation of China (82274358)Shenzhen-Hong Kong Institute of Brain ScienceGuangdong Basic and Applied Basic Research Foundation (2023B1515040009)
文摘Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
基金Key Collaborative Research Program of the Alliance of International Science Organizations(ANSO-CR-KP-2021-12 to L.L.)National Natural Science Foundation of China(32071009,32371063,82341248 to C.L.,31971072 and 32171154 to L.L.)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515011500 to C.L.)Shenzhen Science Technology and Innovative Commission(SZSTI JCYJ20180508152336419 to L.L.and GJHZ20200731095406021 to S.J.)。
文摘The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted to specific organs or tissues.Investigating whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is essential.In this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila melanogaster.Results indicated that the particles caused gut damage and remained within the digestive system.Continuous MP exposure significantly shortened the lifespan of adult flies.Even short-term exposure disrupted sleep patterns,increasing the length of daytime sleep episodes.Additionally,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated females.Although MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these tissues.In the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related pathways.In the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism.Overall,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.
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partly National Key R&D Program of China(2023YFA1801200,2023YFA1801202)Major Program of the National Natural Science Foundation of China(T2394532)+6 种基金National Natural Science Foundation of China(82072489)The Foundation of Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019007)Shenzhen Medical Research Fund(B2302011)The Sanming Project of Medicine in Shenzhen(SZZYSM202311013)The China Postdoctoral Science Foundational,2023M743679Shenzhen Science and Technology Research Funding(JCYJ20220818101414032)Key Research Project of Science&Technology Department of Sichuan Province,China(2024YFFK0041)。
文摘Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金supported by the STI 2030-Major Project(2021ZD0204400,2022ZD0205203,2021ZD0200104,2022ZD0211900)the Shenzhen Science and Technology Program(RCYX20210706092100003,RCBS20221008093311027)+3 种基金the Shenzhen Medical Research Funds(A2303005)the Youth Innovation Promotion Association CAS(2022367)the National Natural Science Foundation of China(32100896)NSFC-Guangdong Joint Fund(U20A6005).
文摘Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.
基金Project(LY19C090004)supported by the Natural Science Foundation of Zhejiang Province,ChinaProjects(BK20200710,BK2018077)supported by the Natural Science Foundation of Jiangsu Province,China+1 种基金Project(NHKY-2019-19)supported by the Nanjing Polytechnic Institute Start Fund,ChinaProject(202012920026Y)supported by the Innovation and Entrepreneurship Training Program of Jiangsu Province College Students,China。
文摘Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the neurophysiological properties of single neuron is still unclear.To tackle this issue,different shape GNPs(nanosphere,nanotriakisoctahedron and nanoflower)were synthesized to investigate the effect of GNPs on the voltage-dependent sodium channel and the action potential(AP)of hippocampal CA1 neurons in mice.The results indicated that GNPs inhibited the amplitudes of voltage-gated sodium current(I_(Na))and led to a hyperpolarizing shift in the voltage-dependence curve of both activation and inactivation of I_(Na).GNPs also increased neuronal excitability and altered some properties of AP.Moreover,most alterations in AP properties were observed in nanoflower GNPs treated CA1 neurons,suggesting that the neurotoxicity of gold nanoparticles is surface roughness-dependent.These results may provide a valuable direction in the clinical application of GNPs.
基金supported by the National Natural Science Foundation of China (31630031 and 31930047)the National Science and Technology Innovation 2030-Major Project of China (2022ZD0208300)+1 种基金the Financial Support for Outstanding Talents Training Fund in Shenzhenthe Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2023B1212060055).
文摘The kidneys are essential organs that help maintain homeostasis,and their function is regulated by the neural system.Despite the anatomical multi-synaptic connection between the central autonomic nuclei and the kidneys,it remains unclear whether there are any variations in neural connections between the nervous systems and the renal cortex and medulla in male and female mice.Here,we used the pseudorabies virus to map the central innervation network of the renal cortex and medulla in both sexes.The data revealed that specific brain regions displayed either a contralateral-bias or ipsilateral-bias pattern while kidney-innervating neurons distributed symmetrically in the midbrain and hindbrain.Sex differences were observed in the distribution of neurons connected to the left kidney,as well as those connected to the renal cortex and medulla.Our findings provide a comprehensive understanding of the brain-kidney network in both males and females and may help shed light on gender differences in kidney function and disease susceptibility in humans.
基金supported by the National Natural Science Foundation of China(U20A2017 and 31830037)Guangdong Basic and Applied Basic Research Foundation(2020A1515010785,2020A1515111118,and 2022A1515010134)+5 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2017120)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019009)Shenzhen Technological Research Center for Primate Translational Medicine(F-2021-Z99-504979)the Strategic Research Program of the Chinese Academy of Sciences(XDBS01030100 and XDB32010300)Scientific and Technological Innovation 2030(2021ZD0204300)the Fundamental Research Funds for the Central Universities.
文摘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.
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the Frontier Research Program of Biol and Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(2018GZR110105006)the National Natural ScienceFoundation of China(31900735,82171492,and 81922024)the Science,Technology and Innovation Commission of Shenzhen Municipality(RCJC 20200714114556103 and ZDSYS20190902093601675).
文摘Dear Editor,Alzheimer's disease(AD)is one of the most devastating neurodegenerative disorders and the most common form of dementia.Synaptic loss is a hallmark of AD pathology and exacerbates cognitive impairment[1].Synaptic loss,unlike neuronal loss,is reversible due to the highly dynamic properties of synapses.
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 National Natural Science Foundation of China(U20A2017)the Natural Science Foundation of Guangdong Province(2020A1515010785)+1 种基金the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS,2017120)the CAS International Partnership Program(172644KYSB20170004).
文摘The use of animals in research has long been debated.In particular,the use of nonhuman primates(NHPs)in either basic or applied research is controversial[1,2].The concerns mainly arise from an ethical perspective given the great similarity between NHPs and humans.While this similarity has scientific advantages,it has also raised concerns that experimental primates may experience pain and suffering in ways similar to humans.
基金This Research Highlight was supported by the Science and Technology Funds of Guangdong Province(2009B030801037)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2017120)+1 种基金the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019009)the Strategic Priority Research Program of Chinese Academy of Sciences(XDBS01030100).
文摘The biological basis of consciousness is one of the hardest questions in Science[1].To understand how consciousness arises from physical components,the brain has been studied systematically for decades.Damage to some structures of the brainstem leads to temporary or persistent loss of consciousness,yet damage to other parts of the brain may lead to limited deficits in certain aspects of awareness.
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the National Natural Science Foundation of China(32070985)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT20190018)Shenzhen Key Laboratory of Translational Research for Brain Diseases(ZDSYS20200828154800001)。
文摘During free exploration,the emergence of patterned and sequential behavioral responses to an unknown environment reflects exploration traits and adaptation.However,the behavioral dynamics and neural substrates underlying the exploratory behavior remain poorly understood.We developed computational tools to quantify the exploratory behavior and performed in vivo electrophysiological recordings in a large arena in which mice made sequential excursions into unknown territory.Occupancy entropy was calculated to characterize the cumulative and moment-to-moment behavioral dynamics in explored and unexplored territories.Local field potential analysis revealed that the theta activity in the dorsal hippocampus(d HPC)was highly correlated with the occupancy entropy.Individual d HPC and prefrontal cortex(PFC)oscillatory activities could classify various aspects of free exploration.Initiation of exploration was accompanied by a coordinated decrease and increase in theta activity in PFC and d HPC,respectively.Our results indicate that d HPC and PFC work synergistically in shaping free exploration by modulating exploratory traits during emergence and visits to an unknown environment.
基金supported by grants from the National Natural Science Foundation of China(31930047,31630031)The Strategic Priority Research Program of Chinese Academy of Science(XDB32030100)+6 种基金the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Natural Science Foundation of Guangdong Province(2018A030313439)Key Laboratory of CAS(2019DP173024)the Ten Thousand Talent Program,The Guangdong Special Support Program,Chang Jiang Scholars Program,the International Partnership Program of Chinese Academy of Sciences(172644KYS820170004)the Key-Area Research and Development Program of Guangdong Province(2018B030331001)the Chinese Academy of Sciences Taiwan Young Talent Programme(2018TW2GB0002-Y)the Guangdong Basic and Applied Basic Research Foundation(2021A1515111030).
文摘Dear Editor,The subthalamic nucleus(STN)is a major component of the evolutionarily-conserved basal ganglia structures[1].While the beneficial effects of deep brain stimulation(DBS)of the STN on motor symptoms in patients with Parkinson's disease(PD)are indisputable,several non-motor symptoms can arise following DBS,including elevated depression and perception of fear in addition to altered sleep-wake parameters.
