IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 DOI: 10.1016/j.neuron.2024.10.011

Jenelle L Wallace, Alex A Pollen

引用次数: 0

Failure in a population: Tauopathy disrupts homeostatic set-points in emergent dynamics despite stability in the constituent neurons. 群体失灵：尽管组成神经元保持稳定，但牛磺酸病破坏了突发动力学中的稳态设定点。

IF 3.784 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-09-05 DOI: 10.1016/j.neuron.2024.08.006

James N McGregor, Clayton A Farris, Sahara Ensley, Aidan Schneider, Leandro J Fosque, Chao Wang, Elizabeth I Tilden, Yuqi Liu, Jianhong Tu, Halla Elmore, Keenan D Ronayne, Ralf Wessel, Eva L Dyer, Kiran Bhaskaran-Nair, David M Holtzman, Keith B Hengen

{"title":"Failure in a population: Tauopathy disrupts homeostatic set-points in emergent dynamics despite stability in the constituent neurons.","authors":"James N McGregor, Clayton A Farris, Sahara Ensley, Aidan Schneider, Leandro J Fosque, Chao Wang, Elizabeth I Tilden, Yuqi Liu, Jianhong Tu, Halla Elmore, Keenan D Ronayne, Ralf Wessel, Eva L Dyer, Kiran Bhaskaran-Nair, David M Holtzman, Keith B Hengen","doi":"10.1016/j.neuron.2024.08.006","DOIUrl":"10.1016/j.neuron.2024.08.006","url":null,"abstract":"Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal pairwise interactions and criticality, a homeostatically controlled, ideal computational regime. Deviations in criticality correlated with symptoms, predicted underlying anatomical pathology, occurred in a sleep-wake-dependent manner, and could be used to reliably classify an animal's genotype. This work illustrates how neurodegeneration may disrupt the computational capacity of neurobiological systems.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3567-3584.e5"},"PeriodicalIF":3.784,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146076","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

Gut-induced alpha-Synuclein and Tau propagation initiate Parkinson's and Alzheimer's disease co-pathology and behavior impairments. 肠道诱导的α-突触核蛋白和Tau传播引发帕金森病和阿尔茨海默病的共同病理学和行为障碍。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-09-05 DOI: 10.1016/j.neuron.2024.08.003

Jie Xiang, Jingrong Tang, Fei Kang, Jiajun Ye, Yueying Cui, Zhentao Zhang, Jing Wang, Shengxi Wu, Keqiang Ye

{"title":"Gut-induced alpha-Synuclein and Tau propagation initiate Parkinson's and Alzheimer's disease co-pathology and behavior impairments.","authors":"Jie Xiang, Jingrong Tang, Fei Kang, Jiajun Ye, Yueying Cui, Zhentao Zhang, Jing Wang, Shengxi Wu, Keqiang Ye","doi":"10.1016/j.neuron.2024.08.003","DOIUrl":"10.1016/j.neuron.2024.08.003","url":null,"abstract":"Tau interacts with α-Synuclein (α-Syn) and co-localizes with it in the Lewy bodies, influencing α-Syn pathology in Parkinson's disease (PD). However, whether these biochemical events regulate α-Syn pathology spreading from the gut into the brain remains incompletely understood. Here, we show that α-Syn and Tau co-pathology is spread into the brain in gut-inducible SYN103+/- and/or TAU368+/- transgenic mouse models, eliciting behavioral defects. Gut pathology was initially observed, and α-Syn or Tau pathology was subsequently propagated into the DMV or NTS and then to other brain regions. Remarkably, more extensive spreading and widespread neuronal loss were found in double transgenic mice (Both) than in single transgenic mice. Truncal vagotomy and α-Syn deficiency significantly inhibited synucleinopathy or tauopathy spreading. The α-Syn PET tracer [18F]-F0502B detected α-Syn aggregates in the gut and brain. Thus, α-Syn and Tau co-pathology can propagate from the gut to the brain, triggering behavioral disorders.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3585-3601.e5"},"PeriodicalIF":14.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146077","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

Integration and competition between space and time in the hippocampus. 海马中空间与时间的整合与竞争

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-09-05 DOI: 10.1016/j.neuron.2024.08.007

Shijie Chen, Ning Cheng, Xiaojing Chen, Cheng Wang

引用次数: 0

NMDA receptors regulate the firing rate set point of hippocampal circuits without altering single-cell dynamics. NMDA 受体在不改变单细胞动力学的情况下调节海马回路的点燃率设定点。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-05 DOI: 10.1016/j.neuron.2024.10.014

Antonella Ruggiero, Leore R Heim, Lee Susman, Dema Hreaky, Ilana Shapira, Maxim Katsenelson, Kobi Rosenblum, Inna Slutsky

{"title":"NMDA receptors regulate the firing rate set point of hippocampal circuits without altering single-cell dynamics.","authors":"Antonella Ruggiero, Leore R Heim, Lee Susman, Dema Hreaky, Ilana Shapira, Maxim Katsenelson, Kobi Rosenblum, Inna Slutsky","doi":"10.1016/j.neuron.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.014","url":null,"abstract":"Understanding how neuronal circuits stabilize their activity is a fundamental yet poorly understood aspect of neuroscience. Here, we show that hippocampal network properties, such as firing rate distribution and dimensionality, are actively regulated, despite perturbations and single-cell drift. Continuous inhibition of N-methyl-D-aspartate receptors (NMDARs) ex vivo lowers the excitation/inhibition ratio and network firing rates while preserving resilience to perturbations. This establishes a new network firing rate set point via NMDAR-eEF2K signaling pathway. NMDARs' capacity to modulate and stabilize network firing is mediated by excitatory synapses and the intrinsic excitability of parvalbumin-positive neurons, respectively. In behaving mice, continuous NMDAR blockade in CA1 reduces network firing without altering single-neuron drift or triggering a compensatory response. These findings expand NMDAR function beyond their canonical role in synaptic plasticity and raise the possibility that some NMDAR-dependent behavioral effects are mediated by their unique regulation of population activity set points.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604624","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

Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias. 氧化还原调节、蛋白质 S-亚硝基化和阿尔茨海默氏症及相关痴呆症的突触丧失。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-05 DOI: 10.1016/j.neuron.2024.10.013

Chang-Ki Oh, Tomohiro Nakamura, Xu Zhang, Stuart A Lipton

{"title":"Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias.","authors":"Chang-Ki Oh, Tomohiro Nakamura, Xu Zhang, Stuart A Lipton","doi":"10.1016/j.neuron.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.013","url":null,"abstract":"Redox-mediated posttranslational modification, as exemplified by protein S-nitrosylation, modulates protein activity and function in both health and disease. Here, we review recent findings that show how normal aging, infection/inflammation, trauma, environmental toxins, and diseases associated with protein aggregation can each trigger excessive nitrosative stress, resulting in aberrant protein S-nitrosylation and hence dysfunctional protein networks. These redox reactions contribute to the etiology of multiple neurodegenerative disorders as well as systemic diseases. In the CNS, aberrant S-nitrosylation reactions of single proteins or, in many cases, interconnected networks of proteins lead to dysfunctional pathways affecting endoplasmic reticulum (ER) stress, inflammatory signaling, autophagy/mitophagy, the ubiquitin-proteasome system, transcriptional and enzymatic machinery, and mitochondrial metabolism. Aberrant protein S-nitrosylation and transnitrosylation (transfer of nitric oxide [NO]-related species from one protein to another) trigger protein aggregation, neuronal bioenergetic compromise, and microglial phagocytosis, all of which contribute to the synapse loss that underlies cognitive decline in Alzheimer's disease and related dementias.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604715","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

Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons. 以丘脑室旁神经元为目标的皮质-丘脑回路的功能特性

IF 14.7 1区医学

Neuron Pub Date : 2024-11-02 DOI: 10.1016/j.neuron.2024.10.010

Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte

{"title":"Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons.","authors":"Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte","doi":"10.1016/j.neuron.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.010","url":null,"abstract":"Corticothalamic projections to sensorimotor thalamic nuclei show modest firing rates and serve to modulate the activity of thalamic relay neurons. By contrast, here we find that high-order corticothalamic projections from the prelimbic (PL) cortex to the anterior paraventricular thalamic nucleus (aPVT) maintain high-frequency activity and evoke strong synaptic excitation of aPVT neurons in rats. In a significant fraction of aPVT cells, such high-frequency excitation of PL-aPVT projections leads to a rapid decay of action potential amplitudes, followed by a depolarization block (DB) that strongly limits aPVT maximum firing rates, thereby regulating both defensive and appetitive behaviors in a frequency-dependent manner. Strong inhibitory inputs from the anteroventral portion of the thalamic reticular nucleus (avTRN) inhibit the firing rate of aPVT neurons during periods of high-spike fidelity but restore it during prominent DB, suggesting that avTRN activity can modulate the effects of PL inputs on aPVT firing rates to ultimately control motivated behaviors.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591265","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

Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes. 抑制 RNA 剪接会触发 CHMP7 进入细胞核，影响 TDP-43 的功能，导致 ALS 细胞表型的出现。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-31 DOI: 10.1016/j.neuron.2024.10.007

Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo

{"title":"Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.","authors":"Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo","doi":"10.1016/j.neuron.2024.10.007","DOIUrl":"10.1016/j.neuron.2024.10.007","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564842","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

Zero-shot counting with a dual-stream neural network model. 利用双流神经网络模型进行零点计数。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-29 DOI: 10.1016/j.neuron.2024.10.008

Jessica A F Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian D Sandbrink, Manuela Piazza, Christopher Summerfield

引用次数: 0

Functional architecture of cerebral cortex during naturalistic movie watching. 自然观影过程中大脑皮层的功能结构。

IF 14.7 1区医学

Neuron Pub Date : 2024-10-25 DOI: 10.1016/j.neuron.2024.10.005

Reza Rajimehr, Haoran Xu, Asa Farahani, Simon Kornblith, John Duncan, Robert Desimone

引用次数: 0

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