Pub Date : 2024-07-17DOI: 10.1038/s41593-024-01714-3
Bhanu P. Tewari, AnnaLin M. Woo, Courtney E. Prim, Lata Chaunsali, Dipan C. Patel, Ian F. Kimbrough, Kaliroi Engel, Jack L. Browning, Susan L. Campbell, Harald Sontheimer
Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex. Approximately 95% of holes in the PNNs contain synapses and astrocytic processes expressing Kir4.1, glutamate and GABA transporters. Hence, holes in the PNNs contain tripartite synapses. In the adult mouse brain, PNN degradation causes an expanded astrocytic coverage of the neuronal somata without altering the axon terminals. The loss of PNNs impairs astrocytic transmitter and potassium uptake, resulting in the spillage of glutamate into the extrasynaptic space. Our data show that PNNs and astrocytes cooperate to contain synaptically released signals in physiological conditions. Their combined action is altered in mouse models of Alzheimer’s disease and epilepsy where PNNs are disrupted. Perineuronal nets stabilize synapses inhibiting synaptic plasticity. Here, the authors show that perineuronal nets act as a diffusion barrier facilitating astrocytic clearance of synaptically released ions and neurotransmitters.
{"title":"Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice","authors":"Bhanu P. Tewari, AnnaLin M. Woo, Courtney E. Prim, Lata Chaunsali, Dipan C. Patel, Ian F. Kimbrough, Kaliroi Engel, Jack L. Browning, Susan L. Campbell, Harald Sontheimer","doi":"10.1038/s41593-024-01714-3","DOIUrl":"10.1038/s41593-024-01714-3","url":null,"abstract":"Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex. Approximately 95% of holes in the PNNs contain synapses and astrocytic processes expressing Kir4.1, glutamate and GABA transporters. Hence, holes in the PNNs contain tripartite synapses. In the adult mouse brain, PNN degradation causes an expanded astrocytic coverage of the neuronal somata without altering the axon terminals. The loss of PNNs impairs astrocytic transmitter and potassium uptake, resulting in the spillage of glutamate into the extrasynaptic space. Our data show that PNNs and astrocytes cooperate to contain synaptically released signals in physiological conditions. Their combined action is altered in mouse models of Alzheimer’s disease and epilepsy where PNNs are disrupted. Perineuronal nets stabilize synapses inhibiting synaptic plasticity. Here, the authors show that perineuronal nets act as a diffusion barrier facilitating astrocytic clearance of synaptically released ions and neurotransmitters.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01714-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1038/s41593-024-01715-2
David F. Parks, Aidan M. Schneider, Yifan Xu, Samuel J. Brunwasser, Samuel Funderburk, Danilo Thurber, Tim Blanche, Eva L. Dyer, David Haussler, Keith B. Hengen
The most robust and reliable signatures of brain states are enriched in rhythms between 0.1 and 20 Hz. Here we address the possibility that the fundamental unit of brain state could be at the scale of milliseconds and micrometers. By analyzing high-resolution neural activity recorded in ten mouse brain regions over 24 h, we reveal that brain states are reliably identifiable (embedded) in fast, nonoscillatory activity. Sleep and wake states could be classified from 100 to 101 ms of neuronal activity sampled from 100 µm of brain tissue. In contrast to canonical rhythms, this embedding persists above 1,000 Hz. This high-frequency embedding is robust to substates, sharp-wave ripples and cortical on/off states. Individual regions intermittently switched states independently of the rest of the brain, and such brief state discontinuities coincided with brief behavioral discontinuities. Our results suggest that the fundamental unit of state in the brain is consistent with the spatial and temporal scale of neuronal computation. Parks, Schneider et al. show that brain states like sleep and wake can be reliably detected from milliseconds of neural activity in local regions in mice. Regions can briefly switch states independently, coinciding with fleeting behavioral changes.
{"title":"A nonoscillatory, millisecond-scale embedding of brain state provides insight into behavior","authors":"David F. Parks, Aidan M. Schneider, Yifan Xu, Samuel J. Brunwasser, Samuel Funderburk, Danilo Thurber, Tim Blanche, Eva L. Dyer, David Haussler, Keith B. Hengen","doi":"10.1038/s41593-024-01715-2","DOIUrl":"10.1038/s41593-024-01715-2","url":null,"abstract":"The most robust and reliable signatures of brain states are enriched in rhythms between 0.1 and 20 Hz. Here we address the possibility that the fundamental unit of brain state could be at the scale of milliseconds and micrometers. By analyzing high-resolution neural activity recorded in ten mouse brain regions over 24 h, we reveal that brain states are reliably identifiable (embedded) in fast, nonoscillatory activity. Sleep and wake states could be classified from 100 to 101 ms of neuronal activity sampled from 100 µm of brain tissue. In contrast to canonical rhythms, this embedding persists above 1,000 Hz. This high-frequency embedding is robust to substates, sharp-wave ripples and cortical on/off states. Individual regions intermittently switched states independently of the rest of the brain, and such brief state discontinuities coincided with brief behavioral discontinuities. Our results suggest that the fundamental unit of state in the brain is consistent with the spatial and temporal scale of neuronal computation. Parks, Schneider et al. show that brain states like sleep and wake can be reliably detected from milliseconds of neural activity in local regions in mice. Regions can briefly switch states independently, coinciding with fleeting behavioral changes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1038/s41593-024-01697-1
Chunyang Dong, Raajaram Gowrishankar, Yihan Jin, Xinyi Jenny He, Achla Gupta, Huikun Wang, Nilüfer Sayar-Atasoy, Rodolfo J. Flores, Karan Mahe, Nikki Tjahjono, Ruqiang Liang, Aaron Marley, Grace Or Mizuno, Darren K. Lo, Qingtao Sun, Jennifer L. Whistler, Bo Li, Ivone Gomes, Mark Von Zastrow, Hugo A. Tejeda, Deniz Atasoy, Lakshmi A. Devi, Michael R. Bruchas, Matthew R. Banghart, Lin Tian
Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions. Dong et al. developed and validated κLight, δLight and µLight, a suite of genetically encoded opioid peptide sensors for probing opioid drugs and brain-region/circuit-specific opioid release in behaving animals.
神经肽在神经系统中无处不在。对神经肽的研究一直受限于缺乏实验工具，无法以特定回路的方式精确剖析神经肽复杂多样的动态变化。阿片肽能调节疼痛、奖赏和厌恶，因此具有很高的临床意义。为了阐明内源性阿片信号在大脑中的时空动态，我们开发了一类基于 kappa、delta 和 mu 阿片受体的基因编码荧光传感器：它们分别是κLight、δLight 和 µLight。我们确定了这些传感器在哺乳动物细胞和离体神经元中的药理学特征。我们利用κLight确定了触发内源性阿片类物质释放的电刺激参数，以及脑切片中达莫啡肽体积传递的时空尺度。通过在小鼠体内使用纤维光度计，我们证明了这些传感器在检测光遗传驱动的阿片类物质释放方面的实用性，并观察到了阿片类物质在恐惧和奖励条件下的不同释放动态。
{"title":"Unlocking opioid neuropeptide dynamics with genetically encoded biosensors","authors":"Chunyang Dong, Raajaram Gowrishankar, Yihan Jin, Xinyi Jenny He, Achla Gupta, Huikun Wang, Nilüfer Sayar-Atasoy, Rodolfo J. Flores, Karan Mahe, Nikki Tjahjono, Ruqiang Liang, Aaron Marley, Grace Or Mizuno, Darren K. Lo, Qingtao Sun, Jennifer L. Whistler, Bo Li, Ivone Gomes, Mark Von Zastrow, Hugo A. Tejeda, Deniz Atasoy, Lakshmi A. Devi, Michael R. Bruchas, Matthew R. Banghart, Lin Tian","doi":"10.1038/s41593-024-01697-1","DOIUrl":"10.1038/s41593-024-01697-1","url":null,"abstract":"Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions. Dong et al. developed and validated κLight, δLight and µLight, a suite of genetically encoded opioid peptide sensors for probing opioid drugs and brain-region/circuit-specific opioid release in behaving animals.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01697-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-11DOI: 10.1038/s41593-024-01725-0
Independent of its appetite- and body weight-modulating effects, the hormone asprosin activates its receptor PTPRD at cerebellar Purkinje neurons to enhance thirst and maintain fluid homeostasis. Surprisingly, this has no effect whatsoever on Purkinje neuron-mediated motor coordination and learning.
{"title":"Cerebellar Purkinje neurons enhance thirst via asprosin–PTPRD signaling","authors":"","doi":"10.1038/s41593-024-01725-0","DOIUrl":"10.1038/s41593-024-01725-0","url":null,"abstract":"Independent of its appetite- and body weight-modulating effects, the hormone asprosin activates its receptor PTPRD at cerebellar Purkinje neurons to enhance thirst and maintain fluid homeostasis. Surprisingly, this has no effect whatsoever on Purkinje neuron-mediated motor coordination and learning.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1038/s41593-024-01700-9
Ila Mishra, Bing Feng, Bijoya Basu, Amanda M. Brown, Linda H. Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C. Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V. Sillitoe, Yanlin He, Atul R. Chopra
The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin’s dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin–Ptprd signaling may be a potential therapeutic target for the management of thirst disorders. Chopra and colleagues show that the hormone asprosin, independent of its effects on hypothalamic AgRP neurons, activates its cell surface receptor Ptprd on cerebellar Purkinje neurons to enhance thirst for maintenance of fluid homeostasis.
{"title":"The cerebellum modulates thirst","authors":"Ila Mishra, Bing Feng, Bijoya Basu, Amanda M. Brown, Linda H. Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C. Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V. Sillitoe, Yanlin He, Atul R. Chopra","doi":"10.1038/s41593-024-01700-9","DOIUrl":"10.1038/s41593-024-01700-9","url":null,"abstract":"The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin’s dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin–Ptprd signaling may be a potential therapeutic target for the management of thirst disorders. Chopra and colleagues show that the hormone asprosin, independent of its effects on hypothalamic AgRP neurons, activates its cell surface receptor Ptprd on cerebellar Purkinje neurons to enhance thirst for maintenance of fluid homeostasis.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141566306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1038/s41593-024-01708-1
Luis A. Mejia
{"title":"Real control in virtual rats","authors":"Luis A. Mejia","doi":"10.1038/s41593-024-01708-1","DOIUrl":"10.1038/s41593-024-01708-1","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1038/s41593-024-01668-6
Laura N. Driscoll, Krishna Shenoy, David Sussillo
Flexible computation is a hallmark of intelligent behavior. However, little is known about how neural networks contextually reconfigure for different computations. In the present work, we identified an algorithmic neural substrate for modular computation through the study of multitasking artificial recurrent neural networks. Dynamical systems analyses revealed learned computational strategies mirroring the modular subtask structure of the training task set. Dynamical motifs, which are recurring patterns of neural activity that implement specific computations through dynamics, such as attractors, decision boundaries and rotations, were reused across tasks. For example, tasks requiring memory of a continuous circular variable repurposed the same ring attractor. We showed that dynamical motifs were implemented by clusters of units when the unit activation function was restricted to be positive. Cluster lesions caused modular performance deficits. Motifs were reconfigured for fast transfer learning after an initial phase of learning. This work establishes dynamical motifs as a fundamental unit of compositional computation, intermediate between neuron and network. As whole-brain studies simultaneously record activity from multiple specialized systems, the dynamical motif framework will guide questions about specialization and generalization. The authors identify reusable ‘dynamical motifs’ in artificial neural networks. These motifs enable flexible recombination of previously learned capabilities, promoting modular, compositional computation and rapid transfer learning. This discovery sheds light on the fundamental building blocks of intelligent behavior.
{"title":"Flexible multitask computation in recurrent networks utilizes shared dynamical motifs","authors":"Laura N. Driscoll, Krishna Shenoy, David Sussillo","doi":"10.1038/s41593-024-01668-6","DOIUrl":"10.1038/s41593-024-01668-6","url":null,"abstract":"Flexible computation is a hallmark of intelligent behavior. However, little is known about how neural networks contextually reconfigure for different computations. In the present work, we identified an algorithmic neural substrate for modular computation through the study of multitasking artificial recurrent neural networks. Dynamical systems analyses revealed learned computational strategies mirroring the modular subtask structure of the training task set. Dynamical motifs, which are recurring patterns of neural activity that implement specific computations through dynamics, such as attractors, decision boundaries and rotations, were reused across tasks. For example, tasks requiring memory of a continuous circular variable repurposed the same ring attractor. We showed that dynamical motifs were implemented by clusters of units when the unit activation function was restricted to be positive. Cluster lesions caused modular performance deficits. Motifs were reconfigured for fast transfer learning after an initial phase of learning. This work establishes dynamical motifs as a fundamental unit of compositional computation, intermediate between neuron and network. As whole-brain studies simultaneously record activity from multiple specialized systems, the dynamical motif framework will guide questions about specialization and generalization. The authors identify reusable ‘dynamical motifs’ in artificial neural networks. These motifs enable flexible recombination of previously learned capabilities, promoting modular, compositional computation and rapid transfer learning. This discovery sheds light on the fundamental building blocks of intelligent behavior.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01668-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1038/s41593-024-01706-3
Thomas C. Brown, Emily C. Crouse, Cecilia A. Attaway, Dana K. Oakes, Sarah W. Minton, Bart G. Borghuis, Aaron W. McGee
To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits. The authors test the model that microglia are crucial for the developmental refinement of neural circuitry by depleting them with PLX5622. Microglia prove dispensable for the experience-dependent maturation of visual circuitry during development.
{"title":"Microglia are dispensable for experience-dependent refinement of mouse visual circuitry","authors":"Thomas C. Brown, Emily C. Crouse, Cecilia A. Attaway, Dana K. Oakes, Sarah W. Minton, Bart G. Borghuis, Aaron W. McGee","doi":"10.1038/s41593-024-01706-3","DOIUrl":"10.1038/s41593-024-01706-3","url":null,"abstract":"To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits. The authors test the model that microglia are crucial for the developmental refinement of neural circuitry by depleting them with PLX5622. Microglia prove dispensable for the experience-dependent maturation of visual circuitry during development.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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