Lingyu Xu

Zhejiang Chinese Medical University

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Zhong Chen

Zhejiang University

Yi Wang

Zhejiang University

Yanrong Zheng

Zhejiang Chinese Medical University

Wenkai Lin

Zhejiang Chinese Medical University

Weiwei Hu

Zhejiang University

Na Tan

Zhejiang University

Yi Guo

Second Affiliated Hospital of Zhejiang University

Zhuowen Fang

Zhejiang University

Lan Yu

Zhejiang Chinese Medical University

Cenglin Xu

Zhejiang University

Cooperative Institutions

Zhejiang University

Zhejiang Chinese Medical University

Second Affiliated Hospital of Zhejiang University

Chinese Academy of Medical Sciences & Peking Union Medical College

Huazhong University of Science and Technology

Capital Medical University

Peking University

Fudan University

Wuhan National Laboratory for Optoelectronics

Xi'an Jiaotong University

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Whole-brain mapping of histaminergic projections in mouse brain

Proceedings of the National Academy of Sciences (2023)

Wenkai Lin Lingyu Xu Yanrong Zheng Sile An Mengting Zhao

Histamine is a conserved neuromodulator in mammalian brains and critically involved in many physiological functions. Understanding the precise structure of the histaminergic network is the cornerstone in elucidating its function. Herein, using histidine decarboxylase (HDC)-CreERT2 mice and genetic labeling strategies, we reconstructed a whole-brain three dimensional (3D) structure of histaminergic neurons and their outputs at 0.32 × 0.32 × 2 μm 3 pixel resolution with a cutting-edge fluorescence microoptical sectioning tomography system. We quantified the fluorescence density of all brain areas and found that histaminergic fiber density varied significantly among brain regions. The density of histaminergic fiber was positively correlated with the amount of histamine release induced by optogenetic stimulation or physiological aversive stimulation. Lastly, we reconstructed a fine morphological structure of 60 histaminergic neurons via sparse labeling and uncovered the largely heterogeneous projection pattern of individual histaminergic neurons. Collectively, this study reveals an unprecedented whole-brain quantitative analysis of histaminergic projections at the mesoscopic level, providing a foundation for future functional histaminergic study.

Histaminergic

Histidine decarboxylase

Agmatine

10.1073/pnas.2216231120

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Citations (26)

Histamine-tuned subicular circuit mediates alert-driven accelerated locomotion in mice

Nature Communications (2024)

Lin Yang Mengdi Zhang Yuan Zhou Dongxiao Jiang Lan Yu

The locomotive action involves diverse coordination, necessitating the integration of multiple motor neural circuits. However, the precise circuitry mechanism governing emotion-driven accelerated locomotion remains predominantly elusive. Here we dissect projections from the tuberomammillary nucleus (TMN) to subiculum (SUB) which promote alert-driven accelerated locomotion. We find that TMN histaminergic neurons respond to high-speed locomotion in both natural and alert acceleration. The TMN-SUB circuit is sufficient but not essential for amplifying accelerated locomotion from low to high-speed movement in basal condition, but it is both sufficient and necessary in alert condition for modulating accelerated locomotion during high-speed escape behavior. TMN histaminergic neuron activates SUB glutamatergic "fast locomotor cell" that projects to retrosplenial granular cortex (RSG) mainly through histamine H2 receptor (H2R). This study reveals the critical role of the histamine-tuned SUB circuit in alert-driven accelerated locomotion in mice, providing a theoretical foundation for comprehending neural circuit mechanisms of instinctive behaviors under alert. The circuitry mechanism governing alert-driven accelerated locomotion remains unclear. Here, the authors report that a histamine-tuned subicular circuit plays a critical role in alert-driven accelerated locomotion in mice.

10.1038/s41467-024-54347-2

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A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy

Nature Communications (2020)

Bin Chen Cenglin Xu Yi Wang Wenkai Lin Ying Wang

The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy.

10.1038/s41467-020-14648-8

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Citations (91)

Lateral Hypothalamus Calcium/Calmodulin-Dependent Protein Kinase II α Neurons Encode Novelty-Seeking Signals to Promote Predatory Eating

Research (2022)

Na Tan Jiaying Shi Lingyu Xu Yanrong Zheng Xia Wang

Predatory hunting is an innate appetite-driven and evolutionarily conserved behavior essential for animal survival, integrating sequential behaviors including searching, pursuit, attack, retrieval, and ultimately consumption. Nevertheless, neural circuits underlying hunting behavior with different features remain largely unexplored. Here, we deciphered a novel function of lateral hypothalamus (LH) calcium/calmodulin-dependent protein kinase II α (CaMKII α + ) neurons in hunting behavior and uncovered upstream/downstream circuit basis. LH CaMKII α + neurons bidirectionally modulate novelty-seeking behavior, predatory attack, and eating in hunting behavior. LH CaMKII α + neurons integrate hunting-related novelty-seeking information from the medial preoptic area (MPOA) and project to the ventral periaqueductal gray (vPAG) to promote predatory eating. Our results demonstrate that LH CaMKII α + neurons are the key hub that integrate MPOA-conveyed novelty-seeking signals and encode predatory eating in hunting behavior, which enriched the neuronal substrate of hunting behavior.

Calcium imaging

Neural substrate

ENCODE

10.34133/2022/9802382

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The Diverse Network of Brain Histamine in Feeding: Dissect its Functions in a Circuit-Specific Way

Current Neuropharmacology (2022)

Lingyu Xu Wenkai Lin Yanrong Zheng Yi Wang Zhong Chen

Feeding is an intrinsic and important behavior regulated by complex molecular, cellular and circuit-level mechanisms, one of which is the brain histaminergic network. In the past decades, many studies have provided a foundation of knowledge about the relationship between feeding and histamine receptors, which are deemed to have therapeutic potential but are not successful in treating feeding- related diseases. Indeed, the histaminergic circuits underlying feeding are poorly understood and characterized. This review describes current knowledge of histamine in feeding at the receptor level. Further, we provide insight into putative histamine-involved feeding circuits based on the classic feeding circuits. Understanding the histaminergic network in a circuit-specific way may be therapeutically relevant for increasing the drug specificity and precise treatment in feeding-related diseases.

Histaminergic

Neuronal Circuits

Biological neural network

10.2174/1570159x21666221117153755

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Citations (3)

An H2R-dependent medial septum histaminergic circuit mediates feeding behavior

Current Biology (2022)

Lingyu Xu Wenkai Lin Yanrong Zheng Jialu Chen Zhuowen Fang

Histaminergic

Premovement neuronal activity

10.1016/j.cub.2022.03.010

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Citations (16)