Progress in Neurobiology最新文献

{"title":"Effect of Electrical Stimulation on Remyelination in Preclinical Models of Multiple Sclerosis: A Systematic Review.","authors":"Abdulrahman Alderei, Poorna Manasa Bhamidimarri, Charalampos Pitsalidis, Ahmed F Yousef, Habiba Al Safar, Shadi W Hasan, Hamdan Hamdan","doi":"10.1016/j.pneurobio.2026.102967","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2026.102967","url":null,"abstract":"<p><strong>Background: </strong>Different types of electrical stimulations (ES), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and peripheral nerve stimulation (PNS) have emerged as neuromodulatory treatments to promote remyelination in multiple sclerosis (MS). Although preclinical evidence continues to accumulate, a systematic review assessing the effect of ES on remyelination across MS-relevant models has not been undertaken.</p><p><strong>Methods: </strong>PubMed-MEDLINE, Embase, and Scopus databases were systematically searched up to January 2026 for in vivo studies investigating ES in demyelinating animal models. Two reviewers independently extracted data on study design, stimulation parameters, and quantitative measures of myelin integrity, including visual evoked potential (VEP) latency, and histological myelin content outcomes. Risk of bias was assessed using SYRCLE's tool.</p><p><strong>Results: </strong>Six eligible studies met the inclusion criteria, comprising EAE, cuprizone, and lysolecithin lesion models. Across these studies, ES was associated with improvements in indices of remyelination, evidenced by reduced VEP latency, and increased myelin protein expression. Effects of tDCS depended on polarity and timing, with anodal stimulation supporting oligodendrocyte maturation during recovery and cathodal stimulation attenuating glial activation during inflammation. VNS promoted remyelination through anti-inflammatory and trophic signaling, and PNS supported spinal remyelination via peripheral to central neuroimmune modulation.</p><p><strong>Conclusion: </strong>Limited but convergent preclinical evidence suggests ES may enhance remyelination by modulating neuronal and inflammatory pathways. However, standardized protocols of stimulation and multimodal imaging studies are needed for clinical translation in MS.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102967"},"PeriodicalIF":4.6,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300193","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}

{"title":"Mechanisms and therapeutic strategies for central and peripheral remyelination.","authors":"Jiangshan Zhan, Juyeon Jo, Carlo D Cristobal, Da Jeong Jeong, Hwan Tae Park, Hyun Kyoung Lee","doi":"10.1016/j.pneurobio.2026.102964","DOIUrl":"10.1016/j.pneurobio.2026.102964","url":null,"abstract":"<p><p>Myelin sheaths are produced by myelinating glia and provide metabolic support to neuronal axons while accelerating electrical signal conduction. Myelinating glia, which include oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS), have distinct developmental origins and biological characteristics that profoundly influence their capacity for myelin regeneration following demyelinating insults. In various demyelinating diseases, loss of myelin and myelinating glia resulting from autoimmune disorders, inflammation, or genetic defects causes neurological dysfunction. Beyond removing disease-causing factors, inducing and accelerating remyelination represents a critical therapeutic goal for demyelinating diseases. In this review, we first summarize and compare molecular mechanisms underlying CNS and PNS remyelination, including extracellular signaling pathways, transcriptional regulation, and intercellular communication. We then highlight current treatments and ongoing clinical trials for common demyelination disorders, including neonatal white matter injury, multiple sclerosis, and inherited peripheral neuropathies.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102964"},"PeriodicalIF":4.6,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149272643","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}

{"title":"Strategy-dependent coding of reward and delay during temporal discounting in macaque dorsolateral prefrontal cortex.","authors":"Rossella Falcone, Siyu Wang, David B Weintraub, Mariko McDougall, Mark A G Eldridge, Barry J Richmond","doi":"10.1016/j.pneurobio.2026.102963","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2026.102963","url":null,"abstract":"<p><p>Some rewards are worth the wait, while others are not. This behavior is governed by temporal discounting, whereby delays reduce the value of future rewards, such that only sufficiently large rewards justify long waits. Individuals differ widely in their strategies to weigh temporally delayed rewards. Prefrontal neurons are known to encode reward and delay; however, it remains unclear whether these neural representations reflect a common temporal discounting computation process, or whether they depend on the individual behavioral strategies for trading off reward and time. We trained two monkeys to choose whether to accept or reject delayed reward offers by releasing a lever at different times contingent on a go signal. We analyzed how the unforeseen go signals, which introduced different additional delays before an offer can be accepted, changed animals' temporal discounting decisions. Behavioral modeling revealed that the two monkeys adopted distinct strategies in re-evaluating the original reward offer in response to the go signal. Monkey S re-calculated the discounted value of the original offer by accounting for the additional delay associated with the go signal, whereas Monkey T treated the go signal as having additive values without re-evaluating the original offer. Although neurons in the dorsolateral prefrontal cortex (dlPFC) of both monkeys encoded reward and delay, we found important differences in how neurons represented these factors, which reflected monkeys' respective behavioral strategies. Our results revealed a strategy-dependent coding of reward and delay in dlPFC.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102963"},"PeriodicalIF":4.6,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149272661","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}

{"title":"Mechanisms of Seizure Generation and SUDEP in Cortical Dysplasia: A Role for Cortical Up and Down States.","authors":"Chih-Hong Lee, Jia-Pei Hong, Siew-Na Lim, Tai-Erh Li, Ting-Wei Liao, Chun-Wei Chang, Bo-Xuan Chen, Hsiang-Han Chen","doi":"10.1016/j.pneurobio.2026.102965","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2026.102965","url":null,"abstract":"<p><p>Sudden unexpected death in epilepsy (SUDEP) remains the primary cause of epilepsy-related mortality, yet the preictal brain dynamics that distinguish fatal from nonfatal seizures are not well understood. Identifying the network mechanisms determining these outcomes is critical for developing SUDEP risk biomarkers. Using a neuron-specific PTEN knockout mouse model of cortical dysplasia-which exhibits spontaneous seizures and SUDEP-like events-we employed long-term video-EEG monitoring to analyze cortical state transitions and network signatures. We found that nonfatal seizures are preceded by a progressive \"ramp-up\" of cortical up and down states, characterized by alternating neuronal depolarization and hyperpolarization, which appears to facilitate seizure initiation. In sharp contrast, sudden death is preceded by a marked suppression of these state transitions and the emergence of infraslow EEG activity, suggestive of spreading depolarizations. This pattern differed from the sustained spike-wave complexes and preserved state transitions observed during status epilepticus. These physiological differences are mirrored behaviorally: nonfatal events typically feature forelimb clonus and spike-wave discharges, whereas fatal seizures are characterized by kicking, tonic hindlimb extension, and diffuse EEG attenuation. Together, these findings suggest that cortical up and down states support seizure initiation, while their disruption and failure to recover postictally predisposes neocortical networks to spreading depression episodes that very likely propagate to brainstem circuits, ultimately triggering SUDEP. By delineating these divergent peri-ictal signatures, this study identifies candidate neurophysiological markers for SUDEP risk stratification.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102965"},"PeriodicalIF":4.6,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246224","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}

{"title":"The cellular basis of rapid human face categorization.","authors":"Marie-Alphée Laurent, Corentin Jacques, Xiaoqian Yan, Pauline Jurczynski, Sophie Colnat-Coulbois, Benoit R Cottereau, Laurent Koessler, Jacques Jonas, Bruno Rossion","doi":"10.1016/j.pneurobio.2026.102966","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2026.102966","url":null,"abstract":"<p><p>Humans readily identify sensory patterns as faces in the environment, yet the neuronal mechanisms underlying rapid face categorization remain unclear. We report the recording of spiking activity inside the face-selective midfusiform gyrus ('Fusiform Face Area', FFA) of 8 human participants to natural images of faces inserted every five stimuli in a fast (6Hz) train of non-face objects. Objective identification of periodic firing rates reveals 81% of visually responsive frequency-tagged neurons (N = 375), with 85% showing significant differential activity between faces and objects (i.e., 6Hz/5 = 1.2Hz). About half of these face-selective neurons are face-exclusive, firing only to faces (i.e., no 6Hz response). Face-selectivity is expressed both as spike increases and decreases of roughly similar proportions, but fewer face-exclusive neurons showing decreases. Cellular face-selective activity shows consistent time-courses across neurons, emerging shortly after 100 ms and lasting for about 210 ms, defining the minimal neuronal discharge time for full face categorization. These findings provide unique insights into the neural basis of rapid human face categorization, highlighting its diverse cellular manifestations.</p>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":" ","pages":"102966"},"PeriodicalIF":4.6,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246159","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}

{"title":"Afferent and efferent projections of parvalbumin-expressing neurons in the thalamic reticular nucleus of the mouse","authors":"Yi-Yao Li,&nbsp;Xin-Tong Qiu,&nbsp;Xiao Ren,&nbsp;Han-Jie Wang,&nbsp;Yu-Tong Guo,&nbsp;Zi-Yan Wang,&nbsp;Lv-La Pan,&nbsp;Fei Li,&nbsp;Tian-Yu Zhao,&nbsp;Fu-Xing Zhang,&nbsp;Yun-Qing Li,&nbsp;Ming-Ming Zhang","doi":"10.1016/j.pneurobio.2026.102942","DOIUrl":"10.1016/j.pneurobio.2026.102942","url":null,"abstract":"<div><div>The whole-brain connectivity of thalamic reticular nucleus (TRN) parvalbumin-positive (PV⁺) neurons has been characterized at the population level, yet their single-cell projectome diversity and the corresponding electrophysiological heterogeneity remain incompletely understood. In this study, we systematically characterized the three-dimensional whole-brain projection patterns and electrophysiological properties of TRN^PV neurons in PV-Cre mice via neural circuit tracing, high-definition fluorescence micro-optical sectioning tomography, and whole-cell patch-clamp recordings. Our findings revealed that these neurons receive extensive cortical inputs, primarily projecting to the dorsal thalamus with region-specific distribution patterns. Notably, ventral TRN^PV neurons preferentially target first-order thalamic nuclei and display higher intrinsic excitability, while dorsal TRN^PV neurons project to higher-order thalamic nuclei with lower excitability — a dorsoventral functional gradient that extends the PV⁺/SOM⁺ projection dichotomy to a continuous spatial axis within the PV⁺ population at single-cell resolution. These findings establish a topographically organized cortex–TRN–thalamus regulatory framework and provide a mechanistic basis for understanding sensory gating and thalamocortical dysregulation in neuropsychiatric disorders.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"263 ","pages":"Article 102942"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550088","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}

{"title":"Corrigendum to “Cortical hyperexcitability drives dying forward amyotrophic lateral sclerosis symptoms and pathology in mice”[Prog. Neurobiol. 252 (2025) 102809]","authors":"Mouna Haidar ,&nbsp;Aida Viden ,&nbsp;Christin Daniel ,&nbsp;Brittany Cuic ,&nbsp;Taide Wang ,&nbsp;Marius Rosier ,&nbsp;Doris Tomas ,&nbsp;Samuel A. Mills ,&nbsp;Alistair Govier-Cole ,&nbsp;Elvan Djouma ,&nbsp;Nirma D. Perera ,&nbsp;Sophia Luikinga ,&nbsp;Valeria Rytova ,&nbsp;Samantha K. Barton ,&nbsp;David G. Gonsalvez ,&nbsp;Lucy M. Palmer ,&nbsp;Catriona McLean ,&nbsp;Matthew C. Kiernan ,&nbsp;Steve Vucic ,&nbsp;Bradley J. Turner","doi":"10.1016/j.pneurobio.2026.102910","DOIUrl":"10.1016/j.pneurobio.2026.102910","url":null,"abstract":"","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"260 ","pages":"Article 102910"},"PeriodicalIF":6.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575205","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}

{"title":"ABCA7 deficiency exacerbates glutamate excitotoxicity in Alzheimer’s disease mice – A new pharmacological target for Glu-related neurotoxicity","authors":"Anna Maria Górska ,&nbsp;Irene Santos-García ,&nbsp;Aleš Kvasnička ,&nbsp;Dana Dobešová ,&nbsp;David Friedecký ,&nbsp;Jacob Gildenblat ,&nbsp;Jens Pahnke","doi":"10.1016/j.pneurobio.2026.102891","DOIUrl":"10.1016/j.pneurobio.2026.102891","url":null,"abstract":"<div><div>Increasing attention has been directed towards the perturbation of glutamate (Glu) and γ-aminobutyric acid (GABA) homeostasis during the pathogenesis of Alzheimer's disease (AD). The prevailing disequilibrium, stemming from hyperactivation of the glutamatergic system, culminates in progressive neuronal impairment and cognitive deterioration. This study aimed to elucidate the contributory role of the ATP-binding cassette transporter A7 (ABCA7), identified as the second most critical genetic determinant in AD, in glutamatergic-associated neurotoxicity. This endeavor sought to advance molecular comprehension of neurological disorders where Glu-GABA neurotransmission represents a pivotal pharmacotherapeutic target. Utilizing multi-omics approaches, we rigorously analyzed four distinct mouse models, both with and without APPtg and ABCA7 expression, to simulate varied pathological and ABCA7-deficient states. Our results revealed amyloid-beta (Aβ) deposition as a catalyst for surging glutamatergic transmission. Notably, ABCA7 ablation exacerbated glutamatergic-induced neurotoxicity, attributed to diminished enzymatic activity related to neurotransmitter degradation and amplified expression levels of specific neurotransmitter transport proteins and receptor subunits, notably NMDA, AMPA, and GABA_A. These findings furnish the first comprehensive description elucidating ABCA7's amplification of neurotoxic effects through modulation of Glu-GABA neurotransmission systems in neurodegenerative contexts, primarily mediated by lipid interaction. The evidence underscores ABCA7's imperative role in shaping future pharmacological strategies aimed at counteracting neurodegeneration precipitated by Glu-mediated neurotoxicity. This research advances the frontier for therapeutic exploration to ameliorate the deleterious neural consequences characteristic of neurodegenerative pathologies.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"259 ","pages":"Article 102891"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133096","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}

{"title":"The flexible synapse – How mossy fiber architecture adapts to changing needs","authors":"Felicitas Bruentgens ,&nbsp;Dietmar Schmitz ,&nbsp;Marta Orlando","doi":"10.1016/j.pneurobio.2026.102882","DOIUrl":"10.1016/j.pneurobio.2026.102882","url":null,"abstract":"<div><div>Hippocampal mossy fiber boutons are unique, highly plastic synapses within the hippocampal circuitry. Despite mossy fiber bouton’s potential role in learning and memory processes, the precise underlying mechanisms leading to their strengthened synaptic connections are still not fully understood. Here, we provide an overview of the structural changes occurring during long-term potentiation of large presynaptic terminals formed by mossy fiber onto CA3 pyramidal cells. Such changes encompass (1) adaptations in the number, shape and size of the bouton; (2) changes in availability of synaptic vesicles as well as the number and occupancy of release sites within single boutons; and (3) nano-architectural changes in the molecular composition and spatial arrangements within active zones. We describe these changes and possible implications for mossy fiber function. Furthermore, we discuss open questions, current methodology, and possible future directions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"258 ","pages":"Article 102882"},"PeriodicalIF":6.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053508","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}

{"title":"Sustained inhibitory dysfunction in complement component C1qa-deficient mice underlies epilepsy and comorbidities","authors":"Joseane Righes Marafiga ,&nbsp;Thy Vu ,&nbsp;Jessica Bowlus ,&nbsp;Scott C. Baraban","doi":"10.1016/j.pneurobio.2026.102881","DOIUrl":"10.1016/j.pneurobio.2026.102881","url":null,"abstract":"<div><div>Neuronal networks undergo critical refinement throughout development and adulthood to maintain proper brain function. Dysregulation of complement component C1qa—including both up- and downregulation—has been linked to circuit dysfunction and neurological disorders such as epilepsy, primarily through effects on excitatory synapses. However, the impact of C1qa downregulation on inhibitory circuits remains poorly understood. We show that germline deletion of C1qa disrupts layer 6 somatostatin (SST)-expressing interneurons in the somatosensory cortex, which we propose underlies enhanced excitatory synaptic transmission, electrographic spike-and-wave discharges, anxiety-like behavior, and impaired sensory-driven behavior. Transplantation of medial ganglionic eminence (MGE)-derived interneuron precursors rescued behavioral deficits but did not abolish the seizure phenotype, underscoring the critical role of C1qa in maintaining inhibitory network integrity—while also suggesting that additional mechanisms beyond interneuron dysfunction contribute to the pathophysiology of absence seizures.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"258 ","pages":"Article 102881"},"PeriodicalIF":6.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990743","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}