IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-01-14 DOI: 10.1016/j.neuron.2024.12.016

Emmy Li, Camila Benitez, Steven C Boggess, Mark Koontz, Indigo V L Rose, Delsy Martinez, Nina Dräger, Olivia M Teter, Avi J Samelson, Na'im Pierce, Erik M Ullian, Martin Kampmann

{"title":"CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions.","authors":"Emmy Li, Camila Benitez, Steven C Boggess, Mark Koontz, Indigo V L Rose, Delsy Martinez, Nina Dräger, Olivia M Teter, Avi J Samelson, Na'im Pierce, Erik M Ullian, Martin Kampmann","doi":"10.1016/j.neuron.2024.12.016","DOIUrl":"10.1016/j.neuron.2024.12.016","url":null,"abstract":"The complexity of the human brain makes it challenging to understand the molecular mechanisms underlying brain function. Genome-wide association studies have uncovered variants associated with neurological phenotypes. Single-cell transcriptomics have provided descriptions of changes brain cells undergo during disease. However, these approaches do not establish molecular mechanism. To facilitate the scalable interrogation of causal molecular mechanisms in brain cell types, we developed a 3D co-culture system of induced pluripotent stem cell (iPSC)-derived neurons and glia, termed iAssembloids. Using iAssembloids, we ask how glial and neuronal cells interact to control neuronal death and survival. Our CRISPRi-based screens identified that GSK3β inhibits the protective NRF2-mediated oxidative stress response elicited by high neuronal activity. We then investigate the role of APOE-ε4, a risk variant for Alzheimer's disease, on neuronal survival. We find that APOE-ε4-expressing astrocytes may promote neuronal hyperactivity as compared with APOE-ε3-expressing astrocytes. This platform allows for the unbiased identification of mechanisms of neuron-glia cell interactions.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"701-718.e8"},"PeriodicalIF":14.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009075","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}

引用次数: 0

Neuronal mechanisms of nociceptive-evoked gamma-band oscillations in rodents. 啮齿动物痛觉诱发伽马波段振荡的神经元机制

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-01-13 DOI: 10.1016/j.neuron.2024.12.011

Lupeng Yue, Chongyu Bao, Libo Zhang, Fengrui Zhang, Wenqian Zhou, Gian Domenico Iannetti, Li Hu

{"title":"Neuronal mechanisms of nociceptive-evoked gamma-band oscillations in rodents.","authors":"Lupeng Yue, Chongyu Bao, Libo Zhang, Fengrui Zhang, Wenqian Zhou, Gian Domenico Iannetti, Li Hu","doi":"10.1016/j.neuron.2024.12.011","DOIUrl":"10.1016/j.neuron.2024.12.011","url":null,"abstract":"Gamma-band oscillations (GBOs) in the primary somatosensory cortex (S1) play key roles in nociceptive processing. Yet, one crucial question remains unaddressed: what neuronal mechanisms underlie nociceptive-evoked GBOs? Here, we addressed this question using a range of somatosensory stimuli (nociceptive and non-nociceptive), neural recording techniques (electroencephalography in humans and silicon probes and calcium imaging in rodents), and optogenetics (alone or simultaneously with electrophysiology in mice). We found that (1) GBOs encoded pain intensity independent of stimulus intensity in humans, (2) GBOs in S1 encoded pain intensity and were triggered by spiking of S1 interneurons, (3) parvalbumin (PV)-positive interneurons preferentially tracked pain intensity, and critically, (4) PV S1 interneurons causally modulated GBOs and pain-related behaviors for both thermal and mechanical pain. These findings provide causal evidence that nociceptive-evoked GBOs preferentially encoding pain intensity are generated by PV interneurons in S1, thereby laying a solid foundation for developing GBO-based targeted pain therapies.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"769-784.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984342","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}

引用次数: 0

Postprandial parasympathetic signals promote lung type 2 immunity. 餐后副交感神经信号促进肺2型免疫。

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-01-20 DOI: 10.1016/j.neuron.2024.12.020

Hongjie Chen, Xin Zhou, Tingting Liu, Jiaqi Liu, Di Wu, Xia Xu, Shanwu Ma, Guangliang Qiang, Jian Chen, Ying Cao, Wei Fu, Jing Yang

{"title":"Postprandial parasympathetic signals promote lung type 2 immunity.","authors":"Hongjie Chen, Xin Zhou, Tingting Liu, Jiaqi Liu, Di Wu, Xia Xu, Shanwu Ma, Guangliang Qiang, Jian Chen, Ying Cao, Wei Fu, Jing Yang","doi":"10.1016/j.neuron.2024.12.020","DOIUrl":"10.1016/j.neuron.2024.12.020","url":null,"abstract":"Lung type 2 immunity protects against pathogenic infection, but its dysregulation causes asthma. Although it has long been observed that symptoms of asthmatic patients often become exaggerated following food intake, the pathophysiological mechanism underlying this postprandial phenomenon is incompletely understood. Here, we report that lung type 2 immunity in mice is enhanced after feeding, which correlates with parasympathetic activation. Also, local parasympathetic innervations exhibit spatial engagement with such immune responses mediated by group 2 innate lymphoid cells (ILC2s). Pharmacologic or surgical blockage of parasympathetic signals diminishes lung type 2 immunity. Conversely, chemogenetic manipulation of parasympathetic inputs and their upstream neurocircuit is sufficient to modulate those immune responses. We then show that the cholinergic receptor muscarinic 4 (Chrm4) for the parasympathetic neurotransmitter acetylcholine is expressed in mouse or human lung ILC2s, and the Chrm4 deletion mitigates ILC2-mediated lung inflammation. These results have revealed a critical neuroimmune function of the gut-brain-lung reflex.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"670-683.e7"},"PeriodicalIF":14.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009080","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}

引用次数: 0

The dynamic axon initial segment: From neuronal polarity to network homeostasis.

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-02-12 DOI: 10.1016/j.neuron.2025.01.004

Amélie Fréal, Casper C Hoogenraad

引用次数: 0

Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment. 细胞内蛋白-脂质相互作用在神经蛋白募集之前驱动突触前组装。

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-01-14 DOI: 10.1016/j.neuron.2024.12.017

Elisa B Frankel, Araven Tiroumalechetty, Zhaoqian Su, Parise S Henry, Brian D Mueller, Erik M Jorgensen, Yinghao Wu, Peri T Kurshan

{"title":"Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment.","authors":"Elisa B Frankel, Araven Tiroumalechetty, Zhaoqian Su, Parise S Henry, Brian D Mueller, Erik M Jorgensen, Yinghao Wu, Peri T Kurshan","doi":"10.1016/j.neuron.2024.12.017","DOIUrl":"10.1016/j.neuron.2024.12.017","url":null,"abstract":"Neurexin cell-adhesion molecules regulate synapse development and function by recruiting synaptic components. Here, we uncover a mechanism for presynaptic assembly that precedes neurexin recruitment, mediated by interactions between cytosolic proteins and membrane phospholipids. Developmental imaging in C. elegans reveals that the intracellular active zone protein SYD-1 accumulates at nascent presynapses prior to its binding partner neurexin. Combining molecular dynamics simulations to model intrinsic interactions between SYD-1 and lipid bilayers with biochemical and in vivo validation of these predictions, we find that PIP2-interacting residues in the SYD-1 C2 domain are required for active zone assembly. Genetic perturbation of a PIP2-generating enzyme disrupts synaptic SYD-1 accumulation, while the PIP2-interacting domain of mammalian RIM1 can compensate for the SYD-1 C2 domain, suggesting functional homology between these proteins. Finally, we propose that the evolutionarily conserved γ-neurexin isoform represents a minimal neurexin sequence that stabilizes nascent presynaptic assemblies, potentially a core function of this isoform.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"737-753.e6"},"PeriodicalIF":14.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009078","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}

引用次数: 0

ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease. ApoE3 R136S与Tau结合并阻断其繁殖，抑制阿尔茨海默病小鼠的神经变性。

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-01-14 DOI: 10.1016/j.neuron.2024.12.015

Guiqin Chen, Mengmeng Wang, Zhentao Zhang, Dae Ki Hong, Eun Hee Ahn, Xia Liu, Seong Su Kang, Keqiang Ye

引用次数: 0

Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns. 纹状体中多巴胺D1受体的激活足以驱动先前皮层模式的强化。

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 Epub Date: 2025-01-14 DOI: 10.1016/j.neuron.2024.12.013

Nuria Vendrell-Llopis, Jonathan Read, Samantha Boggiano, Belinda Hetzler, Zisis Peitsinis, Cherise Stanley, Meike Visel, Dirk Trauner, Prashant Donthamsetti, Jose Carmena, Stephan Lammel, Ehud Y Isacoff

{"title":"Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns.","authors":"Nuria Vendrell-Llopis, Jonathan Read, Samantha Boggiano, Belinda Hetzler, Zisis Peitsinis, Cherise Stanley, Meike Visel, Dirk Trauner, Prashant Donthamsetti, Jose Carmena, Stephan Lammel, Ehud Y Isacoff","doi":"10.1016/j.neuron.2024.12.013","DOIUrl":"10.1016/j.neuron.2024.12.013","url":null,"abstract":"Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood. Using our cell-specific D1R photo-agonist, we find that D1R activation in D1-expressing neurons in the dorsomedial striatum is sufficient to reinforce preceding neural firing patterns in defined ensembles of layer 5 cortico-striatal neurons of the mouse motor cortex. The reinforcement is cumulative and time dependent, with an optimal effect when D1R activation follows the selected neural pattern after a short interval. Our results show that D1R activation in striatal neurons can selectively reinforce cortical activity patterns, independent of a behavioral outcome or a reward, crucially contributing to the fundamental mechanisms that support cognitive functions like learning, memory, and decision-making.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"785-794.e9"},"PeriodicalIF":14.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009076","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}

引用次数: 0

Primary ciliary protein kinase A activity in the prefrontal cortex modulates stress in mice.

IF 14.7 1区医学

Neuron Pub Date : 2025-03-05 DOI: 10.1016/j.neuron.2025.02.002

Jiajun Yang, Yingjie Dong, Jie Liu, Yuwei Peng, Ding Wang, Lei Li, Xiaoqing Hu, Jinfeng Li, Liang Wang, Jun Chu, Jian Ma, Hang Shi, Song-Hai Shi

{"title":"Primary ciliary protein kinase A activity in the prefrontal cortex modulates stress in mice.","authors":"Jiajun Yang, Yingjie Dong, Jie Liu, Yuwei Peng, Ding Wang, Lei Li, Xiaoqing Hu, Jinfeng Li, Liang Wang, Jun Chu, Jian Ma, Hang Shi, Song-Hai Shi","doi":"10.1016/j.neuron.2025.02.002","DOIUrl":"10.1016/j.neuron.2025.02.002","url":null,"abstract":"Primary cilia are cellular antennae emanating from vertebrate cell surfaces to sense and transduce extracellular signals intracellularly to regulate cell behavior and function. However, their signal sensing and physiological functions in neocortical neurons remain largely unclear. Here, we show that, in response to various animal stressors, primary cilia in the mouse prefrontal cortex (PFC) exhibit consistent axonemal elongation. Selective removal of excitatory neuron primary cilia in the prefrontal but not sensory cortex leads to a reduction in animal stress sensing and response. Treatment with corticosterone, the major stress hormone, elicits an increase in primary ciliary cyclic adenosine 3',5'-monphosphate (cAMP) level in PFC excitatory neurons and a decrease in neuronal excitability dependent on primary cilia. Suppression of primary ciliary protein kinase A (PKA) activity in PFC excitatory neurons reduces animal stress. These results suggest that excitatory neurons in the PFC are involved in sensing and regulating animal stress via primary ciliary cAMP/PKA signaling.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582349","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}

引用次数: 0

Sequential transitions of male sexual behaviors driven by dual acetylcholine-dopamine dynamics.

IF 14.7 1区医学

Neuron Pub Date : 2025-03-03 DOI: 10.1016/j.neuron.2025.01.032

Ai Miyasaka, Takeshi Kanda, Naoki Nonaka, Yuka Terakoshi, Yoan Cherasse, Yukiko Ishikawa, Yulong Li, Hotaka Takizawa, Arisa Hirano, Jun Seita, Masashi Yanagisawa, Takeshi Sakurai, Katsuyasu Sakurai, Qinghua Liu

{"title":"Sequential transitions of male sexual behaviors driven by dual acetylcholine-dopamine dynamics.","authors":"Ai Miyasaka, Takeshi Kanda, Naoki Nonaka, Yuka Terakoshi, Yoan Cherasse, Yukiko Ishikawa, Yulong Li, Hotaka Takizawa, Arisa Hirano, Jun Seita, Masashi Yanagisawa, Takeshi Sakurai, Katsuyasu Sakurai, Qinghua Liu","doi":"10.1016/j.neuron.2025.01.032","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.01.032","url":null,"abstract":"The neural mechanisms underlying the sequential transitions of male sexual behaviors, including mounting, intromission, and ejaculation, remain largely unexplored. Here, we report that acetylcholine (ACh)-dopamine (DA) dynamics in the ventral shell of the nucleus accumbens (vsNAc) regulate these sexual transitions in male mice. During intromission, the vsNAc displays a unique pattern of dual ACh-DA rhythms, generated by reciprocal regulation between ACh and DA signaling via nicotinic ACh receptors (nAChRs) and DA D2 receptors (D2Rs). Knockdown of choline acetyltransferase (ChAT) or D2R in the vsNAc diminishes the occurrence of intromission and ejaculation. Optogenetic manipulations demonstrated that DA signaling maintains sexual behaviors by suppressing D2RvsNAc neurons. Moreover, ACh signaling promotes the initiation of mounting and intromission and facilitates the intromission-ejaculation transition by inducing a slowdown in DA rhythm. Together, these findings reveal that coordinated ACh-DA dynamics in the vsNAc play a critical role in orchestrating the sequential transitions of male sexual behaviors.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670164","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}

引用次数: 0

Strategies for mitigating data heterogeneities in AI-based neuro-disease detection.

IF 14.7 1区医学

Neuron Pub Date : 2025-02-25 DOI: 10.1016/j.neuron.2025.01.028

Matthew Leming, Kyungsu Kim, Rose Bruffaerts, Hyungsoon Im

引用次数: 0

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