Progress in Neurobiology最新文献

Understanding the complex interplay between tau, amyloid and the network in the spatiotemporal progression of Alzheimer's Disease.

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-17 DOI: 10.1016/j.pneurobio.2025.102750

Ashish Raj, Justin Torok, Kamalini Ranasinghe

{"title":"Understanding the complex interplay between tau, amyloid and the network in the spatiotemporal progression of Alzheimer's Disease.","authors":"Ashish Raj, Justin Torok, Kamalini Ranasinghe","doi":"10.1016/j.pneurobio.2025.102750","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2025.102750","url":null,"abstract":"<p><strong>Introduction: </strong>The interaction of amyloid and tau in neurodegenerative diseases is a central feature of AD pathophysiology. While experimental studies point to various interaction mechanisms, their causal direction and mode (local, remote or network-mediated) remain unknown in human subjects. The aim of this study was to compare mathematical reaction-diffusion models encoding distinct cross-species couplings to identify which interactions were key to model success.</p><p><strong>Methods: </strong>We tested competing mathematical models of network spread, aggregation, and amyloid-tau interactions on publicly available data from ADNI.</p><p><strong>Results: </strong>Although network spread models captured the spatiotemporal evolution of tau and amyloid in human subjects, the model including a one-way amyloid-to-tau aggregation interaction performed best.</p><p><strong>Discussion: </strong>This mathematical exposition of the \"pas de deux\" of co-evolving proteins provides quantitative, whole-brain support to the concept of amyloid-facilitated-tauopathy rather than the classic amyloid-cascade or pure-tau hypotheses, and helps explain certain known but poorly understood aspects of AD.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102750"},"PeriodicalIF":6.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Astrocytic EphB3 receptors regulate d-serine-gated synaptic plasticity and memory

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-11 DOI: 10.1016/j.pneurobio.2025.102747

Valentin Clément Langlais , Sarah Mountadem , Ines Benazzouz , Aurélie Amadio , Marco Matos , Aurélie Jourdes , Astrid Cannich , Francisca Julio-Kalajzic , Ilaria Belluomo , Isabelle Matias , Marlène Maitre , Thierry Lesté-Lasserre , Sébastien Marais , Elena Avignone , Giovanni Marsicano , Luigi Bellocchio , Stéphane Henri Richard Oliet , Aude Panatier

{"title":"Astrocytic EphB3 receptors regulate d-serine-gated synaptic plasticity and memory","authors":"Valentin Clément Langlais , Sarah Mountadem , Ines Benazzouz , Aurélie Amadio , Marco Matos , Aurélie Jourdes , Astrid Cannich , Francisca Julio-Kalajzic , Ilaria Belluomo , Isabelle Matias , Marlène Maitre , Thierry Lesté-Lasserre , Sébastien Marais , Elena Avignone , Giovanni Marsicano , Luigi Bellocchio , Stéphane Henri Richard Oliet , Aude Panatier","doi":"10.1016/j.pneurobio.2025.102747","DOIUrl":"10.1016/j.pneurobio.2025.102747","url":null,"abstract":"<div><div>The activation of classical NMDA receptors (NMDARs) requires the binding of a co-agonist in addition to glutamate. Whereas astrocytic-derived <span>d</span>-serine was shown to play such a role at CA3-CA1 hippocampal synapses, the exact mechanism by which neurons interact with neighboring astrocytes to regulate synaptic <span>d</span>-serine availability remains to be fully elucidated. Considering the close anatomical apposition of astrocytic and neuronal elements at synapses, the aforementioned process is likely to involve cells adhesion molecules. One very likely candidate could be the astrocytic EphB3 receptor and its neuronal partner, ephrinB3. Here, we first showed in acute hippocampal slices from adult mice that stimulation of EphB3 receptors with exogenous ephrinB3 increased <span>d</span>-serine availability at CA3-CA1 synapses, resulting in an increased NMDAR activity. Conversely, inhibiting endogenous EphB3 receptors caused an impairment of both synaptic NMDAR activity and NMDAR-dependent long-term synaptic potentiation (LTP), effects that could be rescued by exogenous <span>d</span>-serine. Most interestingly, knocking down EphB3 receptors specifically in astrocytes yielded a similar impairment in hippocampal plasticity and, most importantly, caused a deficit in novel object recognition memory. Altogether, our data thus indicate that EphB3 receptors in hippocampal astrocytes play a key role in regulating synaptic NMDAR function, activity-dependent plasticity and memory.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"248 ","pages":"Article 102747"},"PeriodicalIF":6.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Anatomo-functional organization of insular networks: From sensory integration to behavioral control

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-11 DOI: 10.1016/j.pneurobio.2025.102748

Luciano Simone , Fausto Caruana , Borra Elena , Simone Del Sorbo , Ahmad Jezzini , Stefano Rozzi , Giuseppe Luppino , Marzio Gerbella

{"title":"Anatomo-functional organization of insular networks: From sensory integration to behavioral control","authors":"Luciano Simone , Fausto Caruana , Borra Elena , Simone Del Sorbo , Ahmad Jezzini , Stefano Rozzi , Giuseppe Luppino , Marzio Gerbella","doi":"10.1016/j.pneurobio.2025.102748","DOIUrl":"10.1016/j.pneurobio.2025.102748","url":null,"abstract":"<div><div>Classically, the insula is considered an associative multisensory cortex where emotional awareness emerges through the integration of interoceptive and exteroceptive information, along with autonomic regulation. However, since early intracortical microstimulation (ICMS) studies, the insular cortex has also been conceived as a mosaic of anatomo-functional sectors processing various types of sensory information to generate specific overt behaviors. Based on this, the insula has been subdivided into distinct functional fields: an anterior field associated with oroalimentary behaviors, a middle field involved dorsally in hand movements and ventrally in emotional reactions, and a posterior field engaged in axial and proximal movements. Nevertheless, the anatomo-functional networks through which these fields produce motor behaviors remain largely unknown. To fill this gap in the present study, we investigated the connectivity of the macaque insula using a multimodal approach which combines resting-state fMRI with data from tract-tracing injections in insular functional fields defined by ICMS, as well as in brain areas known to be connected to the insula and characterized by specific somatotopic organization. The results revealed that each insular functional field takes part in distinct somatotopically organized network modulating specific motor or visceromotor behaviors, extending previous models that subdivide the insula primarily based on the types of interoceptive and exteroceptive information it receives. Our findings posit the various insular sectors as interfaces that synthesize diverse interoceptive and exteroceptive inputs into coherent subjective experiences and decision-making processes, within an embodied and enactive framework, that moves beyond the traditional dichotomy between sensory experience and motor behavior.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102748"},"PeriodicalIF":6.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pathogenic oligomeric Tau alters neuronal RNA processes through the formation of nuclear heteromeric amyloids with RNA-binding protein Musashi1

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-08 DOI: 10.1016/j.pneurobio.2025.102742

Nicha Puangmalai , Abbigael E. Aday , Madison Samples , Nemil Bhatt , Filippa Lo Cascio , Michela Marcatti , Suhyeorn J. Park , Leiana Fung , Cynthia Jerez , Luiz O. Penalva , Yingxin Zhao , Haiping Hao , Doreen Lugano , Rakez Kayed , Mauro Montalbano

{"title":"Pathogenic oligomeric Tau alters neuronal RNA processes through the formation of nuclear heteromeric amyloids with RNA-binding protein Musashi1","authors":"Nicha Puangmalai , Abbigael E. Aday , Madison Samples , Nemil Bhatt , Filippa Lo Cascio , Michela Marcatti , Suhyeorn J. Park , Leiana Fung , Cynthia Jerez , Luiz O. Penalva , Yingxin Zhao , Haiping Hao , Doreen Lugano , Rakez Kayed , Mauro Montalbano","doi":"10.1016/j.pneurobio.2025.102742","DOIUrl":"10.1016/j.pneurobio.2025.102742","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is marked by cytoplasmic proteinopathies, primarily involving misfolded Tau protein. Pathogenic Tau species, such as soluble oligomers and fibrils, disrupt RNA metabolism, though the mechanisms are unclear. Recent research indicates that RNA has a crucial role in Tau aggregation. Our study builds on this by noting significant co-deposition of RNA-Binding Proteins (RBPs) with Tau in AD and Frontotemporal dementia (FTLD) brains. Using molecular and cellular techniques, we investigate the interaction between RNA dynamics and Tau aggregation, focusing on the localization and aggregation of Tau and RBPs, particularly Musashi (MSI), within neuronal nuclei. Through cyto-fluorometric, biochemical, and cellular assays, we reveal the importance of Tau/RBP interplay in primary cortical neurons expressing wild-type and mutant Tau. Pathogenic Tau oligomers alter MSI protein localization and function, causing cytoplasmic and nuclear aggregation. Mass spectrometry of the MSI1 nuclear interactome in Tau models shows disrupted RNA metabolism pathways, including ribosomal biogenesis, RNA splicing, and protein folding. Moreover, RNA immunoprecipitation assay revealed a remarkable impact of mutant P301L Tau on MSI1 ability to bind RNA targets. These findings highlight potential targets for early neurodegenerative therapeutic interventions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102742"},"PeriodicalIF":6.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

NPTX2 transfection improves synaptic E/I balance and performance in learning impaired aged rats

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-07 DOI: 10.1016/j.pneurobio.2025.102746

Daniel Severin , Ming Teng Koh , Cristian Moreno , Darwin Contreras , Altagracia Contreras , Christian Wesselborg , Michelle Bridi , Jala Atufa , Audrey Branch , Paul Worley , Michela Gallagher , Alfredo Kirkwood

{"title":"NPTX2 transfection improves synaptic E/I balance and performance in learning impaired aged rats","authors":"Daniel Severin , Ming Teng Koh , Cristian Moreno , Darwin Contreras , Altagracia Contreras , Christian Wesselborg , Michelle Bridi , Jala Atufa , Audrey Branch , Paul Worley , Michela Gallagher , Alfredo Kirkwood","doi":"10.1016/j.pneurobio.2025.102746","DOIUrl":"10.1016/j.pneurobio.2025.102746","url":null,"abstract":"<div><div>Excessive neural activity in the medial temporal lobe commonly associates with cognitive decline in elderly humans and also in rodents.An attractive model pathway to study synaptic mechanisms underlying age-dependent circuit hyperexcitability is the connection made by lateral entorhinal cortex cells onto the dentate gyrus (LEC→DG). Both structures are particularly affected by age and, importantly, in behaviorally characterized aged rats, learning impairment correlates with diminished feedforward inhibition of granule cells recruited by LEC inputs. In this rat model of aging, we evaluated how overexpression of Neuronal Pentraxin 2 (NPTX2) in the LEC, essential for stabilizing excitatory inputs onto fast-spiking inhibitory interneurons (FS-INs), enhances feedforward inhibition and improves spatial memory in impaired individuals. In addition, we found that FS-INs from unimpaired aged individuals have an increased excitatory drive compared to young individuals. These findings support the notion that NPTX2-mediated compensatory mechanisms to enhance the recruitment of FS-INs are crucial to maintaining proficient memory performance during aging.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102746"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Astrocytic GluN2A alleviates sleep deprivation-induced elevation of Aβ through regulating neprilysin and AQP4 via the calcineurin/NFAT pathway.

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-01 DOI: 10.1016/j.pneurobio.2025.102744

Xiaoqiang Du, Hongqi Wang, Siyu Liu, Yizhi Song, Xinyue Chen, Ziyan Chen, Ruying Zhou, Jiahe Du, Wanning Zhang, Ruiqi Gao, Hui Li, Guitao Zhang, Xin Mao, Lirong Chang, Yan Wu

{"title":"Astrocytic GluN2A alleviates sleep deprivation-induced elevation of Aβ through regulating neprilysin and AQP4 via the calcineurin/NFAT pathway.","authors":"Xiaoqiang Du, Hongqi Wang, Siyu Liu, Yizhi Song, Xinyue Chen, Ziyan Chen, Ruying Zhou, Jiahe Du, Wanning Zhang, Ruiqi Gao, Hui Li, Guitao Zhang, Xin Mao, Lirong Chang, Yan Wu","doi":"10.1016/j.pneurobio.2025.102744","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2025.102744","url":null,"abstract":"<p><p>Sleep disorders can increase amyloid beta (Aβ) burden in the brain and are linked to Alzheimer's disease (AD) risk. The precise mechanism by which sleep disturbances elevate Aβ levels is unclear. Our previous study has demonstrated that knocking down encoding gene Grin2a of astrocytic N-methyl-D-aspartate (NMDA) receptors GluN2A subunit could aggravate sleep deprivation (SD)-induced elevation of Aβ, indicating a protective role of astrocytic GluN2A in SD; but the underlying mechanism needs to be further elucidated. In our present study, using rat models of SD combined with specific astrocytic Grin2a knockdown or overexpression in the hippocampus, and a cell model of primary cultured hippocampal astrocytes, we reveal a novel mechanism that astrocytic GluN2A alleviates SD-induced increases in Aβ. We demonstrated that astrocytic GluN2A mainly affected Aβ degradation and clearance through regulating degradation enzyme neprilysin and Aquaporin-4 (AQP4), via the calcineurin/NFAT pathway. Our study provides supportive evidence for the novel role and mechanism of astrocytic GluN2A in Aβ elimination, which would contribute to the discovery of new therapeutic strategies for Aβ-related diseases such as AD.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102744"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Traumatic brain injury from a peripheral axis perspective: Uncovering the roles of liver and adipose tissue in temperature regulation

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-03-01 DOI: 10.1016/j.pneurobio.2025.102733

F. Gomez-Pinilla , Sydney K. Myers

{"title":"Traumatic brain injury from a peripheral axis perspective: Uncovering the roles of liver and adipose tissue in temperature regulation","authors":"F. Gomez-Pinilla , Sydney K. Myers","doi":"10.1016/j.pneurobio.2025.102733","DOIUrl":"10.1016/j.pneurobio.2025.102733","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Most current treatments for TBI and other neurological disorders focus on the brain, often overlooking the significant contributions of peripheral organs to disease progression. Emerging evidence suggests that organs such as the liver and adipose tissue play crucial roles in TBI pathogenesis. The liver synthesizes lipids and proteins vital for brain function, while adipose tissue provides hormones and metabolites that influence brain activity. New research indicates that the liver and adipose tissue work in concert with the hypothalamus to regulate essential processes, such as body temperature, which become disrupted in TBI. Additionally, the brain-peripheral axis—a complex network of visceral nerve pathways, hormones, and metabolites—plays a bidirectional role in regulating brain plasticity and function. Understanding how TBI leads to dysregulation of the liver, adipose tissue, and other organs could unlock new therapeutic opportunities for treating TBI and related neurological disorders. The intricate autonomic network involving hypothalamic and enteric neurons, along with visceral nerve pathways and hormones, presents both pathological targets and therapeutic potential. We examine scientific evidence suggesting that correcting disturbances in systemic physiology could enhance the brain’s capacity for healing. However, the interdependence of this autonomic network implies that treating dysfunction in one area may affect others. Therefore, we also explore the mechanisms by which diet and exercise can comprehensively impact the brain-peripheral axis, supporting the healing process.</div></div><div><h3>Chemical compounds</h3><div>D-Fructose (PubChem CID 2723872); docosahexaenoic acid (PubChem CID 45934466); eicosapentaenoic acid (PubChem 5282847);</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102733"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Surround modulation is predominantly orientation-unspecific in macaque V1

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-02-28 DOI: 10.1016/j.pneurobio.2025.102745

Xing-Nan Zhao , Sheng-Hui Zhang , Shi-Ming Tang , Cong Yu

{"title":"Surround modulation is predominantly orientation-unspecific in macaque V1","authors":"Xing-Nan Zhao , Sheng-Hui Zhang , Shi-Ming Tang , Cong Yu","doi":"10.1016/j.pneurobio.2025.102745","DOIUrl":"10.1016/j.pneurobio.2025.102745","url":null,"abstract":"<div><div>Surround modulation is a fundamental property of V1 neurons, playing critical roles in stimulus integration and segregation. It is believed to be orientation-specific, as neurons’ responses at preferred orientations are suppressed more by iso-oriented surrounds than by cross-oriented surrounds. Here, we investigated an alternative hypothesis that surround modulation is primarily orientation-unspecific, in that the observed “orientation-specific” surround effects actually reflect overall gain changes that affect neurons tuned to all orientations. We employed two-photon calcium imaging to compare V1 population orientation tuning functions under iso- and cross-surround modulation in awake, fixating macaques. While confirming “orientation-specific” surround suppression in individual neurons, our analysis of the population orientation tuning functions revealed that iso-surrounds induce a general orientation-unspecific suppression across all orientation-tuned neurons, plus weak orientation-specific suppression to neurons tuned to the center stimulus orientation. Furthermore, cross-surrounds mainly reduce orientation-unspecific suppression by scaling up responses of all orientation-tuned neurons. These findings suggest a model of population gain control where surround stimuli mostly scale the responses of the neuronal population. Further population coding analyses supported this conclusion, demonstrating that surround suppression leads to degraded target orientation information at least partially due to a reduced number of contributing neurons with diverse orientation preferences.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102745"},"PeriodicalIF":6.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Current amyloid inhibitors: Therapeutic applications and nanomaterial-based innovations

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-02-28 DOI: 10.1016/j.pneurobio.2025.102734

Paula López-García , María M. Tejero-Ojeda , María Eugenia Vaquero, Mariano Carrión-Vázquez

{"title":"Current amyloid inhibitors: Therapeutic applications and nanomaterial-based innovations","authors":"Paula López-García , María M. Tejero-Ojeda , María Eugenia Vaquero, Mariano Carrión-Vázquez","doi":"10.1016/j.pneurobio.2025.102734","DOIUrl":"10.1016/j.pneurobio.2025.102734","url":null,"abstract":"<div><div>Amyloid proteins have long been in the spotlight for being involved in many degenerative diseases including Alzheimer´s, Parkinson´s or type 2 diabetes, which currently cannot be prevented and for which there is no effective treatment or cure. Here we provide a comprehensive review of inhibitors that act directly on the amyloidogenic pathway (at the monomer, oligomer or fibril level) of key pathological amyloids, focusing on the most representative amyloid-related diseases. We discuss the latest advances in preclinical and clinical trials, focusing on cutting-edge developments, particularly on nanomaterials-based inhibitors, which offer unprecedented opportunities to address the complexity of protein misfolding disorders and are revolutionizing the landscape of anti-amyloid therapeutics. Notably, nanomaterials are impacting critical areas such as bioavailability, penetrability and functionality of compounds currently used in biomedicine, paving the way for more specific therapeutic solutions tailored to various amyloid-related diseases. Finally, we highlight the window of opportunity opened by comparative analysis with so-called functional amyloids for the development of innovative therapeutic approaches for these devastating diseases.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102734"},"PeriodicalIF":6.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Dynamics of hippocampal reactivation for temporal association memory in mice

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-02-27 DOI: 10.1016/j.pneurobio.2025.102729

Hui Chen , Bin Wang , Yue Zhan , Junqi Liu , Sicheng Yang , Xuan Tan , Weiwei Zhang , Jie Zhang , Ye Yang , Yanji Liu , Meilin Wang , Haibo Zhang , Xuan Li , Zhongxiang Yao , Drolma Pema , Hongli Li , Hao Chen , Bo Hu

{"title":"Dynamics of hippocampal reactivation for temporal association memory in mice","authors":"Hui Chen , Bin Wang , Yue Zhan , Junqi Liu , Sicheng Yang , Xuan Tan , Weiwei Zhang , Jie Zhang , Ye Yang , Yanji Liu , Meilin Wang , Haibo Zhang , Xuan Li , Zhongxiang Yao , Drolma Pema , Hongli Li , Hao Chen , Bo Hu","doi":"10.1016/j.pneurobio.2025.102729","DOIUrl":"10.1016/j.pneurobio.2025.102729","url":null,"abstract":"<div><div>Reactivation refers to the re-emergence of activity in neuronal ensembles that were active during information encoding. Hippocampal CA1 neuronal ensembles generate firing activities that encode the temporal association among time-separated events. However, whether and how temporal association memory-related CA1 neuronal ensembles reactivate during sleep and their role in temporal association memory consolidation remain unclear. We utilized multiple unit recordings to monitor CA1 neuronal activity in mice learning a trace eyeblink conditioning (tEBC) task, in which presentation of the conditioned stimulus (CS, a light flash) was paired with presentation of the unconditioned stimulus (US, corneal puff) by a time-separated interval. We found that the CS-US paired training mice exhibited few conditioned eyeblink responses (CRs) at the initial-learning stage (ILS) and an asymptotic level of CRs at the well-learning stage (WLS). More than one third of CA1 pyramidal cells (PYR) in the CS-US paired training mice manifested a CS-evoked firing activity that was sustained from the CS to time-separated interval. The CS-evoked PYR firing activity was required for the tEBC acquisition and was greater when the CRs occurred. Intriguingly, the CS-evoked firing PYR ensembles reactivated, which coincided with increased hippocampal ripples during post-training sleep. The reactivation of CS-evoked firing PYR ensembles diminished across learning stages, with greater strength in the ILS. Disrupting the ripple-associated PYR activity impaired both the reactivation of CS-evoked firing PYR ensembles and tEBC consolidation. Our findings highlight the features of hippocampal CA1 neuronal ensemble reactivation during sleep, which support the consolidation of temporal association memory.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102729"},"PeriodicalIF":6.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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