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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

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Ramping dynamics in the frontal cortex unfold over multiple timescales during motor planning

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Journal of neurophysiology 2025年第2期133卷 625-637页

作者： Affan, Rifqi O. Bright, Ian M. Pemberton, Luke N. Cruzado, Nathanael A. Scott, Benjamin B. Howard, Marc W. Graduate Program in Neuroscience Boston University Boston MA United States Department of Psychological and Brain Sciences Boston University Boston MA United States

Plans are formulated and refined throughout the period leading up to their execution, ensuring that the appropriate behaviors are enacted at the appropriate times. Although existing evidence suggests that memory circuits convey the passage of time through diverse neuronal responses, it remains unclear whether the neural circuits involved in planning exhibit analogous temporal dynamics. Using publicly available data, we analyzed how activity in the mouse frontal motor cortex evolves during motor planning. Individual neurons exhibited diverse ramping activity throughout a delay interval that preceded a planned movement. The collective activity of these neurons was useful for making temporal predictions that became increasingly precise as the movement time approached. This temporal diversity gave rise to a spectrum of encoding patterns, ranging from stable to dynamic representations of the upcoming movement. Our results indicate that ramping activity unfolds over multiple timescales during motor planning, suggesting a shared mechanism in the brain for processing temporal information related to both memories from the past and plans for the future. NEW & NOTEWORTHY Neuronal responses in the cortex are diverse, but the nature and functional consequences of this diversity remain ambiguous. We identified a specific pattern of temporal heterogeneity in the mouse frontal motor cortex, whereby the firing of different neurons ramps up at varying speeds before the execution of a movement. Our decoding analyses reveal that this heterogeneity in ramping dynamics enables precise and reliable encoding of movement plans and time across various timescales.

关键词： frontal cortex motor planning neuronal heterogeneity ramping activity time

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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： Mackenzie M.Spicer Jianqi Yang Daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of Neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa Neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in Molecular Medicine University of Iowa Carver College of MedicineIowa CityIAUSA Neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

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Early auditory and adult mating experiences interact with singer identity to shape neural responses to song in female zebra finches

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Journal of Neurophysiology 2025年第2期133卷 598-610页

作者： Catalano, Isabella Woolley, Sarah C. Integrated Program in Neuroscience McGill University Montreal QC Canada Center for Research on Brain Language and Music Montreal QC Canada Department of Biology McGill University Montreal QC Canada

Social and sensory experiences across the lifespan can shape social interactions;however, experience-dependent plasticity is widely studied within discrete life stages. In the socially monogamous zebra finch, in which females use learned vocal signals to identify individuals and form long-lasting pair bonds, developmental exposure to song is key for females to show species-typical song perception and preferences. Although adult mating experience can still lead to pair-bonding and song preference learning even in birds with limited previous song exposure (“song-naive”), whether similarities in adult behavioral plasticity between normally reared and song-naive females reflect convergent patterns of neural activity is unknown. We investigated this using expression of a marker of neural activity and plasticity [phosphorylated S6 (pS6)] in mated normally reared and song-naive females in response to song from either their mate, a neighbor, or an unfamiliar male. We found that, in portions of a secondary auditory region (the caudomedial nidopallium, NCM) and in dopaminergic neurons of the caudal ventral tegmental area, hearing the mate’s song significantly increased pS6 expression in females from both rearing conditions. In contrast, within other NCM subregions, song identity drove different patterns of pS6 expression depending on the rearing condition. These data suggest that developmental experiences can have long-lasting impacts on the neural signatures of behaviors acquired in adulthood and that socially driven behavioral plasticity in adults may arise through both shared and divergent neural circuits depending on an individual’s developmental experiences. © 2025 the American Physiological Society.

关键词： auditory learning female zebra finch individual recognition learning and memory mate song learning

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Time, control, and the nervous system

arXiv

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arXiv 2025年

作者： Haimerl, Caroline Rodrigues, Filipe S. Paton, Joseph J. Champalimaud Centre for the Unknown Champalimaud Neuroscience Program Portugal

Because organisms are able to sense its passage, it is perhaps tempting to treat time as a sensory modality, akin to vision or audition. Indeed, certain features of sensory estimation, such as Weber’s law, apply to timing and sensation alike (Gibbon, 1977;Pardo-Vazquez et al., 2019). However, from an organismal perspective, time is a derived feature of other signals, not a stimulus that can be readily transduced by sensory receptors. Its importance for biology lies in the fact that the physical world comprises a complex dynamical system. The multiscale spatiotemporal structure of sensory and internally generated signals within an organism is the informational fabric underlying its ability to control behavior. Viewed this way, temporal computations assume a more fundamental role than is implied by treating time as just another element of the experienced world (Paton & Buonomano, 2018). Thus, in this review we focus on temporal processing as a means of approaching the more general problem of how the nervous system produces adaptive behavior. © 2025, CC BY.

关键词： Brain

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Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo Department of Molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA Division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.O’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Neural Correlates of Semantic Interference and Phonological Facilitation in Picture Naming: A Systematic Review and Coordinate-Based Meta-analysis

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NEUROPSYCHOLOGY REVIEW 2025年第1期35卷 35-53页

作者： [Anonymous] PhD Program in Neuroscience School of Medicine and Surgery University of Milano-Bicocca Monza Italy Department of Psychology University of Milano-Bicocca Milan Italy Center for Mind/Brain Sciences (CIMeC) Neurocognitive Rehabilitation Center (CeRiN) University of Trento Rovereto Italy

Semantic interference (SI) and phonological facilitation (PF) effects occur when multiple representations are co-activated simultaneously in complex naming paradigms, manipulating the context in which word production is set. Although the behavioral consequences of these psycholinguistic effects are well-known, the involved brain structures are still controversial. This paper aims to provide a systematic review and a coordinate-based meta-analysis of the available functional neuroimaging studies investigating SI and PF in picture naming paradigms. The included studies were fMRI experiments on healthy subjects, employing paradigms in which co-activations of representations were obtained by manipulating the naming context using semantically or phonologically related items. We examined the principal methodological aspects of the included studies, emphasizing the existing commonalities and discrepancies across single investigations. We then performed an exploratory coordinate-based meta-analysis of the reported activation peaks of neural response related to SI and PF. Our results consolidated previous findings regarding the involvement of the left inferior frontal gyrus and the left middle temporal gyrus in SI and brought out the role of bilateral inferior parietal regions in PF.

关键词： Picture naming Semantic interference Phonological facilitation Meta-analysis fMRI

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