Journal of Comparative Neurology最新文献

{"title":"Brainwide Projections of Mouse Dopaminergic Zona Incerta Neurons","authors":"Bianca S. Bono,&nbsp;Kenichiro Negishi,&nbsp;Yasmina Dumiaty,&nbsp;Monica S. Ponce-Ruiz,&nbsp;Titilayo C. Akinbode,&nbsp;Kayla S. Baker,&nbsp;C. Duncan P. Spencer,&nbsp;Elizabeth Mejia,&nbsp;Marina Guirguis,&nbsp;Alex J. Hebert,&nbsp;Arshad M. Khan,&nbsp;Melissa J. Chee","doi":"10.1002/cne.70039","DOIUrl":"https://doi.org/10.1002/cne.70039","url":null,"abstract":"<p>The zona incerta (ZI) supports diverse behaviors including binge feeding, sleep–wake cycles, nociception, and hunting. Diverse ZI functions can be attributed to its heterogeneous neurochemical characterization, cytoarchitecture, and efferent connections. The ZI is predominantly GABAergic, but we recently identified a subset of medial ZI GABA cells that are marked by the enzyme tyrosine hydroxylase (TH) and produce dopamine (DA). While the role of GABA within the ZI is well studied, less is known about the functions of ZI DA cells. To identify potential roles of ZI DA cells, we further phenotyped them and mapped their efferent fiber projections. We showed that wild-type TH-immunoreactive (-ir) ZI cells did not express somatostatin or calretinin immunoreactivity. We next validated a <i>Th-cre;L10-Egfp</i> mouse line and found that medial <i>Egfp</i> ZI cells were more likely to be TH-ir. We therefore delivered a Cre-dependent virus into the medial ZI of <i>Th-cre</i> or <i>Th-cre;L10-Egfp</i> mice and selected two injection cases for full brain mapping, namely, cases with the lowest and highest colocalization between TH-ir and virally transduced, DsRed-labeled cells, to identify common target sites. Overall, DsRed-labeled fibers were distributed brainwide and were most prominent within the motor-related midbrain (MBmot), notably the periaqueductal gray area and superior colliculus. We also observed numerous DsRed-labeled fibers within the polymodal association cortex-related thalamus (DORpm), like paraventricular thalamic nucleus and nucleus of reunions, that processes external and internal sensory input. Overall, ZI DA cells displayed a similar fiber profile to ZI GABA cells and may integrate sensory input to coordinate motor output at their target sites.</p>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cne.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural Contributions to Extrasynaptic Glutamatergic Signaling in Olfactory Bulb Glomeruli","authors":"Jennifer N. Bourne,&nbsp;Nathan E. Schoppa","doi":"10.1002/cne.70034","DOIUrl":"https://doi.org/10.1002/cne.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Olfactory bulb glomeruli have a complex organization that includes axodendritic synapses between olfactory sensory neurons (OSNs) and excitatory mitral cells (MCs) and tufted cells (TCs), as well as dendrodendritic synapses between MCs/TCs and GABAergic periglomerular cells (PGCs). MCs also receive excitatory signals from one subclass of TCs, the external tufted cells (eTCs). While these signals are driven by glutamate released from eTC dendrites, they appear not to reflect direct eTC &gt; MC synaptic connections but rather “spill-over” of glutamate released at eTC &gt; PGC synapses acting on nearby MC dendrites. Here, we used serial section electron microscopy images of rat olfactory bulb glomeruli with biocytin-labeled MC and eTC dendrites to evaluate potential ultrastructural underpinnings of “extrasynaptic” signaling. We compared the environment around eTC &gt; PGC synapses with that of MC &gt; PGC synapses using several quantitative measures and, as a further point of comparison, also evaluated axodendritic OSN &gt; MC and OSN &gt; eTC synapses. Across the four synapse types, one unique feature of eTC &gt; PGC synapses was their much closer distance to the nearest dendrites of excitatory cells (including MCs), averaging ∼160 nm. In contrast, astroglial processes were positioned quite far away from eTC &gt; PGC synapses, with a mean distance of ∼500 nm. These distance values would suggest that glutamate released from eTC &gt; PGC synapses may access nearby excitatory dendrites without interference from glial glutamate transporters, thus providing an ultrastructural basis for extrasynaptic signaling. Our battery of ultrastructural measures, which included brick analyses, also supported a long-standing model for the organization of glomeruli in which OSN and dendrodendritic synapses are segregated into discrete compartments.</p>\u0000 </div>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSF Workshop Report: Exploring Measurements and Interpretations of Intelligent Behaviors Across Animal Model Systems","authors":"Joseph V. Gogola,&nbsp;Mary Kate Joyce,&nbsp;Susheel Vijayraghavan,&nbsp;George Barnum,&nbsp;Gregg Wildenberg","doi":"10.1002/cne.70035","DOIUrl":"https://doi.org/10.1002/cne.70035","url":null,"abstract":"<p>Defining intelligence is a challenging and fraught task, but one that neuroscientists are repeatedly confronted with. A central goal of neuroscience is to understand how phenomena like intelligent behaviors emerge from nervous systems. This requires some determination of what defines intelligence and how to measure it. The challenge is multifaceted. For instance, as we begin to describe and understand the brain in increasingly specific physical terms (e.g., anatomy, cell types, activity patterns), we amplify an ever-growing divide in how we connect measurable properties of the brain to less tangible concepts like intelligence. As our appreciation for evolutionary diversity in neuroscience grows, we are further confronted with whether there can be a unifying theory of intelligence. The National Science Foundation (NSF) NeuroNex consortium recently gathered experts from multiple animal model systems to discuss intelligence across species. We summarize here the different perspectives offered by the consortium, with the goal of promoting thought and debate of this ancient question from a modern perspective, and asking whether defining intelligence is a useful exercise in neuroscience or an ill-posed and distracting question. We present data from the vantage points of humans, macaques, ferrets, crows, octopuses, bees, and flies, highlighting some of the noteworthy capabilities of each species within the context of each species’ ecological niche and how these may be challenged by climate change. We also include a remarkable example of convergent evolution between primates and crows in the circuit and molecular basis for working memory in these highly divergent animal species.</p>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cne.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of Layer 1 Interneurons in the Mouse Medial Prefrontal Cortex","authors":"Chen Shen,&nbsp;Wanpeng Cui,&nbsp;Wen-Cheng Xiong,&nbsp;Lin Mei","doi":"10.1002/cne.70030","DOIUrl":"https://doi.org/10.1002/cne.70030","url":null,"abstract":"<p>Cortical Layer 1 (L1) acts as a critical relay for processing long-range inputs. GABAergic inhibitory interneurons (INs) in this layer (Layer 1 interneurons [L1INs]) function as inhibitory gates, regulating these inputs and modulating the activity of deeper cortical layers. However, their characteristics and circuits in the medial prefrontal cortex (mPFC) remain poorly understood. Using biocytin labeling, we identified three distinct morphological types of mPFC L1INs: neurogliaform cells (NGCs), elongated NGCs (eNGCs), and single-bouquet cell-like (SBC-like) cells. Whole-cell recordings revealed distinct firing patterns across these subtypes: NGCs and eNGCs predominantly exhibited late-spiking (LS) patterns, and SBC-like cells displayed a higher prevalence of non-LS (NLS) patterns. We observed both electrical and chemical connections among mPFC L1INs. Optogenetic activation of NDNF⁺ L1INs demonstrated broad inhibitory effects on deeper layer neurons. The strength of inhibition on pyramidal neurons (PyNs) and INs displayed layer-specific preference. These findings highlight the functional diversity of L1INs in modulating mPFC circuits and suggest their potential role in supporting higher order cognitive functions.</p>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cne.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 533, Issue 3","authors":"Chen Shen,&nbsp;Wanpeng Cui,&nbsp;Wen-Cheng Xiong,&nbsp;Lin Mei","doi":"10.1002/cne.70037","DOIUrl":"https://doi.org/10.1002/cne.70037","url":null,"abstract":"<p>The cover image is based on the article <i>Heterogeneity of Layer 1 Interneurons in the Mouse Medial Prefrontal Cortex</i> by Lin Mei et al., https://doi.org/10.1002/cne.70030.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cne.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Engulfment of Multisensory Terminals in the Midbrain Inferior Colliculus During an Early Critical Period","authors":"Emily R. Moran,&nbsp;Mark L. Gabriele","doi":"10.1002/cne.70033","DOIUrl":"https://doi.org/10.1002/cne.70033","url":null,"abstract":"<p>The lateral cortex of the inferior colliculus (LCIC) receives multisensory input arrays that preferentially target its compartmental organization. Inputs of somatosensory origin end within modular zones, while auditory inputs terminate throughout an encompassing matrix. Such discrete mapping emerges during an early postnatal critical period (birth to postnatal day 12, P12) via a process of segregation. Similar to other primitive brain maps, it appears an initial excess of connections may be pruned through a refinement process. Microglial cells (MGCs) are involved in a variety of systems in the selective removal and degradation of unnecessary contacts. Aberrations in map plasticity during early critical periods have been associated with certain neurodevelopmental conditions, including autism spectrum disorders (ASD). Despite evidence linking multisensory integration deficits with cognitive/behavioral disturbances associated with ASD, mechanisms that govern multimodal network modifications remain poorly understood. Thus, the present study combines novel tract-tracing approaches in living brain preparations and immunocytochemistry in CX3CR1-GFP knock-in mice to determine: (1) if fractalkine signaling (CX3CL1–CX3CR1) influences MGC engulfment of auditory afferents, (2) whether individual MGCs phagocytose endings of multisensory origin (auditory and somatosensory), and (3) whether consumed product is degraded via the MGC's lysosomal pathway. We demonstrate active MGC pruning of auditory endings at peak LCIC stages for projection shaping (P4, P8) that significantly decreases coincident with its critical period closure (P12). While developmentally regulated, auditory engulfment appears fractalkine signaling-independent. We also provide evidence that individual LCIC microglia engulf both auditory and somatosensory terminals that co-localize with the lysosomal marker, CD68. These results suggest a prominent role for microglia in the remodeling of early multisensory midbrain maps.</p>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cne.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Complexly Parcellated, Yet Quantitatively Reduced, Orexinergic/Hypocretinergic System of Humans","authors":"Illke B. Malungo,&nbsp;Ayanda Ngwenya,&nbsp;Mads F. Bertelsen,&nbsp;Muhammad A. Spocter,&nbsp;Thomas C. Thannickal,&nbsp;Jerome M. Siegel,&nbsp;Paul R. Manger","doi":"10.1002/cne.70032","DOIUrl":"https://doi.org/10.1002/cne.70032","url":null,"abstract":"<p>The phylogenetic contextualization of human neuroanatomy is crucial for understanding the positive, neutral, and/or negative effects of therapeutic interventions derived from animal models. Here we determined the parcellation of, and quantified, orexinergic (or hypocretinergic) neurons in the hypothalami of humans and several species of primates, including strepsirrhines (two species), platyrrhines (two species), cercopithecoids (three species), and hominoids (three species, including humans). The strepsirrhines, platyrrhines, and cercopithecoids presented with three distinct clusters of orexinergic neurons, revealing an organization like that observed in most mammals. In the three hominoids, an additional orexinergic cluster was found in the tuberal region of the hypothalamus, termed the optic tract cluster extension. In humans only, an additional parvocellular cluster of orexinergic neurons was observed in the dorsomedial hypothalamus. The human presented with the most complex parcellation of orexinergic neurons of the primates studied. Total numbers of orexinergic neurons in nonhuman primates were strongly correlated to brain mass (<i>P</i>_uncorr = 1.2 × 10⁻⁶), with every doubling in brain mass leading to an ∼1.5-times increase in neuron number. In contrast, humans have approximately 74,300 orexinergic neurons, which is significantly less than the 205,000 predicted using the nonhuman primate regression for a brain mass of ∼1363 g. We conclude that although the human orexinergic system is the most complex of primates in terms of parcellation, with potential associated functional specializations, this system is quantitatively paradoxical in having a significantly lower neuronal number than expected for a primate with an ∼1363-g brain.</p>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cne.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Fish Neuropeptides: A Novel Perspective on Animal Welfare","authors":"Jose Carlos Campos-Sánchez,&nbsp;María José Cabrera-Álvarez,&nbsp;Joao L. Saraiva","doi":"10.1002/cne.70029","DOIUrl":"https://doi.org/10.1002/cne.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuropeptides are highly variable but widely conserved molecules, the main functions of which are the regulation and coordination of physiological processes and behaviors. They are synthesized in the nervous system and generally act on other neuronal and non-neuronal tissues or organs. In recent years, diverse neuropeptide isoforms and their receptors have been identified in different fish species, regulating functions in the neuroendocrine (e.g., corticotropin-releasing hormone and arginine vasotocin), immune (e.g., vasoactive intestinal polypeptide and somatostatin), digestive (e.g., neuropeptide Y), and reproductive (e.g., isotocin) systems, as well as in the commensal microbiota. Interestingly, all these processes carried out by neuropeptides are integrated into the nervous system and are manifested externally in the behavior and affective states of fish, thus having an impact on the modulation of these actions. In this sense, the monitoring of neuropeptides may represent a new approach to assess animal welfare, targeting both physiological and affective aspects in fish. Therefore, although there are many studies investigating the action of neuropeptides in a wide range of paradigms, especially in mammals, their study within a fish welfare framework is scarce. To the best of our knowledge, this is the first review that gathers and integrates up-to-date information on neuropeptides from an animal welfare perspective. In this review, we summarize current findings on neuropeptides in fish and discuss their possible implication in the physiological and emotional state of fish, and therefore in their welfare.</p>\u0000 </div>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mammalian Retinal Bipolar Cells: Morphological Identification and Systematic Classification in Rabbit Retina With a Comparative Perspective","authors":"Edward V. Famiglietti","doi":"10.1002/cne.70015","DOIUrl":"https://doi.org/10.1002/cne.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>Retinal bipolar cells (BCs) convey visual signals from photoreceptors to more than 50 types of rabbit retinal ganglion cells (Famiglietti, 2020). More than 40 years ago, 10–11 types of bipolar cells were recognized in rabbit and cat retinas (Famiglietti, 1981). Twenty years later, 10 were identified in mouse, rat, and monkey, while recent molecular genetic studies indicate that there are 15 types of bipolar cell in mouse retina (Shekhar et al., 2016). The present detailed study of more than 800 bipolar cells in 11 Golgi-impregnated rabbit retinas indicates that there are 14–16 types of cone bipolar cell and one type of rod bipolar cell in rabbit retina. These have been carefully analyzed in terms of dendritic and axonal morphology and axon terminal stratification with respect to fiducial starburst amacrine cells. In fortuitous proximity, several types of bipolar cell can be related to identified ganglion cells by stratification and by contacts suggestive of synaptic connection. These results are compared with other studies of rabbit bipolar cells. Homologies with bipolar cells of mouse and monkey are considered in functional terms.</p>\u0000 </div>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Synaptic Complexity of a High-Integration Lobula Giant Neuron in Crabs","authors":"Yair Barnatan,&nbsp;Claire Rind,&nbsp;Florencia Scarano,&nbsp;Julieta Sztarker","doi":"10.1002/cne.70026","DOIUrl":"https://doi.org/10.1002/cne.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Arthropods are diverse, abundant, successful animals that exploit all available ecological niches. They sense the environment, move, interact with prey/predators/conspecifics, learn, and so forth using small brains with five orders of magnitude less neurons than mammals. Hence, these brains need to be efficient in information processing. One distinct aspect is the presence of large, easily identifiable single neurons that act as functional units for information processing integrating a high volume of information from different sources to guide behavior. To understand the synaptic organization behind these high-integration nodes research on suitable neurons is needed. The lobula giant neurons (LGs) found in the third optic neuropil, the lobula, of semiterrestrial crabs <i>Neohelice granulata</i> respond to moving stimuli, integrate information from both eyes, and show short- and long-term plasticity. They are thought to be key elements in the visuomotor transformation guiding escape responses to approaching objects. One subgroup, the MLG1 (monostratified LG type 1), is composed of 16 elements that have very wide main branches and a regular arrangement in a deep layer of the lobula which allows their identification even in unstained preparations. Here, we describe the types and abundance of synaptic contacts involving MLG1 profiles using transmission electron microscopy (TEM). We found an unexpected diversity of synaptic motifs and an apparent compartmentalization of the dendritic arbor in two domains where MLG1s act predominantly as presynaptic or postsynaptic, respectively. We propose that the variety of contact types found in the dendritic arbor of the MLG1s reflects the multiple circuits in which these cells are involved. Regarding the detection of approaching objects, the distinctive input contact motifs shared by lobula giant neurons in crabs and locusts suggest a similar organization of the collision-detecting pathways in both species.</p>\u0000 </div>","PeriodicalId":15552,"journal":{"name":"Journal of Comparative Neurology","volume":"533 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}