IF 3.784 1区医学

Neuron Pub Date : 2024-09-24 DOI: 10.1016/j.neuron.2024.09.006

Gillian K Carling, Li Fan, Nessa R Foxe, Kendra Norman, Man Ying Wong, Daphne Zhu, Carlo Corona, Agnese Razzoli, Fangmin Yu, Allan Yarahmady, Pearly Ye, Hao Chen, Yige Huang, Sadaf Amin, Rebecca Sereda, Chloe Lopez-Lee, Emmanouil Zacharioudakis, Xiaoying Chen, Jielin Xu, Feixiong Cheng, Evripidis Gavathiotis, Ana Maria Cuervo, David M Holtzman, Sue-Ann Mok, Subhash C Sinha, Simone Sidoli, Rajiv R Ratan, Wenjie Luo, Shiaoching Gong, Li Gan

{"title":"Alzheimer's disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model.","authors":"Gillian K Carling, Li Fan, Nessa R Foxe, Kendra Norman, Man Ying Wong, Daphne Zhu, Carlo Corona, Agnese Razzoli, Fangmin Yu, Allan Yarahmady, Pearly Ye, Hao Chen, Yige Huang, Sadaf Amin, Rebecca Sereda, Chloe Lopez-Lee, Emmanouil Zacharioudakis, Xiaoying Chen, Jielin Xu, Feixiong Cheng, Evripidis Gavathiotis, Ana Maria Cuervo, David M Holtzman, Sue-Ann Mok, Subhash C Sinha, Simone Sidoli, Rajiv R Ratan, Wenjie Luo, Shiaoching Gong, Li Gan","doi":"10.1016/j.neuron.2024.09.006","DOIUrl":"10.1016/j.neuron.2024.09.006","url":null,"abstract":"The strongest risk factors for late-onset sporadic Alzheimer's disease (AD) include the ε4 allele of apolipoprotein E (APOE), the R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combine APOE4 and TREM2R47H (R47H) in female P301S tauopathy mice to identify the pathways activated when AD risk is the strongest, thereby highlighting detrimental disease mechanisms. We find that R47H induces neurodegeneration in 9- to 10-month-old female APOE4 tauopathy mice. The combination of APOE4 and R47H (APOE4-R47H) worsened hyperphosphorylated tau pathology in the frontal cortex and amplified tauopathy-induced microglial cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling and downstream interferon response. APOE4-R47H microglia displayed cGAS- and BAX-dependent upregulation of senescence, showing association between neurotoxic signatures and implicating mitochondrial permeabilization in pathogenesis. By uncovering pathways enhanced by the strongest AD risk factors, our study points to cGAS-STING signaling and associated microglial senescence as potential drivers of AD risk.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":3.784,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365947","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

Transcriptomic cell-type specificity of local cortical circuits. 局部皮层回路的转录组细胞类型特异性

IF 14.7 1区医学

Neuron Pub Date : 2024-09-24 DOI: 10.1016/j.neuron.2024.09.003

Maribel Patiño, Marley A Rossa, Willian Nuñez Lagos, Neelakshi S Patne, Edward M Callaway

{"title":"Transcriptomic cell-type specificity of local cortical circuits.","authors":"Maribel Patiño, Marley A Rossa, Willian Nuñez Lagos, Neelakshi S Patne, Edward M Callaway","doi":"10.1016/j.neuron.2024.09.003","DOIUrl":"10.1016/j.neuron.2024.09.003","url":null,"abstract":"Complex neocortical functions rely on networks of diverse excitatory and inhibitory neurons. While local connectivity rules between major neuronal subclasses have been established, the specificity of connections at the level of transcriptomic subtypes remains unclear. We introduce single transcriptome assisted rabies tracing (START), a method combining monosynaptic rabies tracing and single-nuclei RNA sequencing to identify transcriptomic cell types, providing inputs to defined neuron populations. We employ START to transcriptomically characterize inhibitory neurons providing monosynaptic input to 5 different layer-specific excitatory cortical neuron populations in mouse primary visual cortex (V1). At the subclass level, we observe results consistent with findings from prior studies that resolve neuronal subclasses using antibody staining, transgenic mouse lines, and morphological reconstruction. With improved neuronal subtype granularity achieved with START, we demonstrate transcriptomic subtype specificity of inhibitory inputs to various excitatory neuron subclasses. These results establish local connectivity rules at the resolution of transcriptomic inhibitory cell types.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365949","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

Distinct circuits and molecular targets of the paraventricular hypothalamus decode visceral and somatic pain. 室旁下丘脑的不同回路和分子靶标对内脏痛和躯体痛进行解码

IF 14.7 1区医学

Neuron Pub Date : 2024-09-21 DOI: 10.1016/j.neuron.2024.08.024

Yong-Chang Li, Fu-Chao Zhang, Di Li, Rui-Xia Weng, Yang Yu, Rong Gao, Guang-Yin Xu

引用次数: 0

A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events. 快速、灵敏的电压指示器，对单元突触事件的灵敏度更高。

IF 3.784 1区医学

Neuron Pub Date : 2024-09-20 DOI: 10.1016/j.neuron.2024.08.019

Yukun A Hao, Sungmoo Lee, Richard H Roth, Silvia Natale, Laura Gomez, Jiannis Taxidis, Philipp S O'Neill, Vincent Villette, Jonathan Bradley, Zeguan Wang, Dongyun Jiang, Guofeng Zhang, Mengjun Sheng, Di Lu, Edward Boyden, Igor Delvendahl, Peyman Golshani, Marius Wernig, Daniel E Feldman, Na Ji, Jun Ding, Thomas C Südhof, Thomas R Clandinin, Michael Z Lin

{"title":"A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events.","authors":"Yukun A Hao, Sungmoo Lee, Richard H Roth, Silvia Natale, Laura Gomez, Jiannis Taxidis, Philipp S O'Neill, Vincent Villette, Jonathan Bradley, Zeguan Wang, Dongyun Jiang, Guofeng Zhang, Mengjun Sheng, Di Lu, Edward Boyden, Igor Delvendahl, Peyman Golshani, Marius Wernig, Daniel E Feldman, Na Ji, Jun Ding, Thomas C Südhof, Thomas R Clandinin, Michael Z Lin","doi":"10.1016/j.neuron.2024.08.019","DOIUrl":"10.1016/j.neuron.2024.08.019","url":null,"abstract":"A remaining challenge for genetically encoded voltage indicators (GEVIs) is the reliable detection of excitatory postsynaptic potentials (EPSPs). Here, we developed ASAP5 as a GEVI with enhanced activation kinetics and responsivity near resting membrane potentials for improved detection of both spiking and subthreshold activity. ASAP5 reported action potentials (APs) in vivo with higher signal-to-noise ratios than previous GEVIs and successfully detected graded and subthreshold responses to sensory stimuli in single two-photon trials. In cultured rat or human neurons, somatic ASAP5 reported synaptic events propagating centripetally and could detect ∼1-mV EPSPs. By imaging spontaneous EPSPs throughout dendrites, we found that EPSP amplitudes decay exponentially during propagation and that amplitude at the initiation site generally increases with distance from the soma. These results extend the applications of voltage imaging to the quantal response domain, including in human neurons, opening up the possibility of high-throughput, high-content characterization of neuronal dysfunction in disease.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":3.784,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292263","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

Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI. 腹侧海马旁白神经元对血清素能迷幻剂 DOI 的急性抗焦虑作用具有把关作用。

IF 14.7 1区医学

Neuron Pub Date : 2024-09-19 DOI: 10.1016/j.neuron.2024.08.016

Praachi Tiwari, Pasha A Davoudian, Darshana Kapri, Ratna Mahathi Vuruputuri, Lindsay A Karaba, Mukund Sharma, Giulia Zanni, Angarika Balakrishnan, Pratik R Chaudhari, Amartya Pradhan, Shital Suryavanshi, Kevin G Bath, Mark S Ansorge, Antonio Fernandez-Ruiz, Alex C Kwan, Vidita A Vaidya

{"title":"Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI.","authors":"Praachi Tiwari, Pasha A Davoudian, Darshana Kapri, Ratna Mahathi Vuruputuri, Lindsay A Karaba, Mukund Sharma, Giulia Zanni, Angarika Balakrishnan, Pratik R Chaudhari, Amartya Pradhan, Shital Suryavanshi, Kevin G Bath, Mark S Ansorge, Antonio Fernandez-Ruiz, Alex C Kwan, Vidita A Vaidya","doi":"10.1016/j.neuron.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.08.016","url":null,"abstract":"There has been a recent renewal of interest in the therapeutic potential of serotonergic psychedelics. Here, we uncover the essential role of ventral hippocampus (vHpc) GABAergic interneurons in the anxiolytic effect evoked by the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Integrating anatomical, pharmacological, and genetic approaches, we show that 5-HT2A receptors in the CA1/subiculum (CA1/sub) region of the vHpc are required for the anxiolytic action of DOI. In vivo electrophysiology and opto-tagging experiments indicate that DOI enhances the firing rate of hippocampal fast-spiking parvalbumin (PV)-positive interneurons, most of which express the 5-HT2A receptors. Restoration of 5-HT2A receptors in PV-positive interneurons in a loss-of-function background reinstated the anxiolytic responses evoked by DOI in the vHpc CA1/sub region. Collectively, our results localize the acute anxiolytic action of a serotonergic psychedelic to 5-HT2A receptors in the ventral hippocampus and specifically identify PV-positive fast-spiking cells as a cellular trigger for the psychedelic-induced relief of anxiety-like behavior.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350990","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 sodium-bicarbonate cotransporter Slc4a5 mediates feedback at the first synapse of vision. 钠-碳酸氢盐共转运体 Slc4a5 在视觉的第一个突触处介导反馈。

IF 14.7 1区医学

Neuron Pub Date : 2024-09-18 DOI: 10.1016/j.neuron.2024.08.015

Rei Morikawa, Tiago M Rodrigues, Helene Marianne Schreyer, Cameron S Cowan, Sarah Nadeau, Alexandra Graff-Meyer, Claudia P Patino-Alvarez, Mohammad Hossein Khani, Josephine Jüttner, Botond Roska

{"title":"The sodium-bicarbonate cotransporter Slc4a5 mediates feedback at the first synapse of vision.","authors":"Rei Morikawa, Tiago M Rodrigues, Helene Marianne Schreyer, Cameron S Cowan, Sarah Nadeau, Alexandra Graff-Meyer, Claudia P Patino-Alvarez, Mohammad Hossein Khani, Josephine Jüttner, Botond Roska","doi":"10.1016/j.neuron.2024.08.015","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.08.015","url":null,"abstract":"Feedback at the photoreceptor synapse is the first neuronal circuit computation in vision, which influences downstream activity patterns within the visual system. Yet, the identity of the feedback signal and the mechanism of synaptic transmission are still not well understood. Here, we combined perturbations of cell-type-specific genes of mouse horizontal cells with two-photon imaging of the result of light-induced feedback in cones and showed that the electrogenic bicarbonate transporter Slc4a5, but not the electroneutral bicarbonate transporter Slc4a3, both expressed specifically in horizontal cells, is necessary for horizontal cell-to-cone feedback. Pharmacological blockage of bicarbonate transporters and buffering pH also abolished the feedback but blocking sodium-proton exchangers and GABA receptors did not. Our work suggests an unconventional mechanism of feedback at the first visual synapse: changes in horizontal cell voltage modulate bicarbonate transport to the cell, via Slc4a5, which leads to the modulation of feedback to cones.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350988","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

An amygdalar oscillator coordinates cellular and behavioral rhythms. 杏仁核振荡器能协调细胞和行为节奏。

IF 14.7 1区医学

Neuron Pub Date : 2024-09-18 DOI: 10.1016/j.neuron.2024.08.013

Qiang Liu, Jiali Xiong, Dong Won Kim, Sang Soo Lee, Benjamin J Bell, Chloe Alexandre, Seth Blackshaw, Alban Latremoliere, Mark N Wu

{"title":"An amygdalar oscillator coordinates cellular and behavioral rhythms.","authors":"Qiang Liu, Jiali Xiong, Dong Won Kim, Sang Soo Lee, Benjamin J Bell, Chloe Alexandre, Seth Blackshaw, Alban Latremoliere, Mark N Wu","doi":"10.1016/j.neuron.2024.08.013","DOIUrl":"10.1016/j.neuron.2024.08.013","url":null,"abstract":"Circadian rhythms are generated by the master pacemaker suprachiasmatic nucleus (SCN) in concert with local clocks throughout the body. Although many brain regions exhibit cycling clock gene expression, the identity of a discrete extra-SCN brain oscillator that produces rhythmic behavior has remained elusive. Here, we show that an extra-SCN oscillator in the lateral amygdala (LA) is defined by expression of the clock-output molecule mWAKE/ANKFN1. mWAKE is enriched in the anterior/dorsal LA (adLA), and, strikingly, selective disruption of clock function or excitatory signaling in adLAmWAKE neurons abolishes Period2 (PER2) rhythms throughout the LA. mWAKE levels rise at night and promote rhythmic excitability of adLAmWAKE neurons by upregulating Ca2+-activated K+ channel activity specifically at night. adLAmWAKE neurons coordinate rhythmic sensory perception and anxiety in a clock-dependent and WAKE-dependent manner. Together, these data reveal the cellular identity of an extra-SCN brain oscillator and suggest a multi-level hierarchical system organizing molecular and behavioral rhythms.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292265","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

Offline hippocampal reactivation during dentate spikes supports flexible memory. 齿状突起时的离线海马再激活支持灵活记忆

IF 14.7 1区医学

Neuron Pub Date : 2024-09-17 DOI: 10.1016/j.neuron.2024.08.022

Stephen B McHugh, Vítor Lopes-Dos-Santos, Manfredi Castelli, Giuseppe P Gava, Sophie E Thompson, Shu K E Tam, Katja Hartwich, Brook Perry, Robert Toth, Timothy Denison, Andrew Sharott, David Dupret

{"title":"Offline hippocampal reactivation during dentate spikes supports flexible memory.","authors":"Stephen B McHugh, Vítor Lopes-Dos-Santos, Manfredi Castelli, Giuseppe P Gava, Sophie E Thompson, Shu K E Tam, Katja Hartwich, Brook Perry, Robert Toth, Timothy Denison, Andrew Sharott, David Dupret","doi":"10.1016/j.neuron.2024.08.022","DOIUrl":"10.1016/j.neuron.2024.08.022","url":null,"abstract":"Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the cornu ammonis (CA) region and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events for supporting this offline process. SWRs have been studied extensively, but the contribution of DSs remains unclear. By combining triple-ensemble (DG-CA3-CA1) recordings and closed-loop optogenetics in mice, we show that, like SWRs, DSs synchronize spiking across DG and CA principal cells to reactivate population-level patterns of neuronal coactivity expressed during prior waking experience. Notably, the population coactivity structure in DSs is more diverse and higher dimensional than that seen during SWRs. Importantly, suppressing DG granule cell spiking selectively during DSs impairs subsequent flexible memory performance during multi-object recognition tasks and associated hippocampal patterns of neuronal coactivity. We conclude that DSs constitute a second offline network event central to hippocampal population dynamics serving memory-guided behavior.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350986","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

Ventral frontostriatal circuitry mediates the computation of reinforcement from symbolic gains and losses. 前额纹状体腹侧回路介导了对象征性收益和损失的强化计算。

IF 14.7 1区医学

Neuron Pub Date : 2024-09-17 DOI: 10.1016/j.neuron.2024.08.018

Hua Tang, Ramon Bartolo, Bruno B Averbeck

引用次数: 0

Plaudits for logits in sensory neuroscience. 为感觉神经科学中的对数点赞。

IF 14.7 1区医学

Neuron Pub Date : 2024-09-04 DOI: 10.1016/j.neuron.2024.08.008

Joshua J H Ryu, Justin L Gardner

引用次数: 0

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