Progress in Neurobiology最新文献

{"title":"Orthogonal neural geometry of orientation, spatial frequency, and ocular dominance in macaque V1","authors":"Xin Wang ,&nbsp;Sheng-Hui Zhang ,&nbsp;Shi-Ming Tang ,&nbsp;Cong Yu","doi":"10.1016/j.pneurobio.2025.102874","DOIUrl":"10.1016/j.pneurobio.2025.102874","url":null,"abstract":"<div><div>The classical ice-cube model of Hubel and Wiesel proposes that V1 neurons are spatially organized into orthogonal maps of orientation and ocular dominance to optimize wiring efficiency. However, extending this framework to include additional features such as spatial frequency imposes constraints on how these features can be spatially arranged on the cortical surface. A recent two-photon imaging study of ours found that cellular-resolution maps of orientation, spatial frequency, and ocular dominance in macaque V1 lack consistent orthogonal or parallel spatial arrangements. To investigate whether these features are instead represented in population activity space, we applied principal component analysis (PCA) to these and additional datasets. We found that population responses formed near-orthogonal geometries in representational space, supporting the idea that feature encoding relies more on population-level activity than spatial layout. This orthogonal structure remained robust to dimensionality changes and was absent in response-shuffled control data, in which feature axes collapsed to chance-level alignment. Furthermore, artificially disrupting orthogonality, either by aligning feature axes or randomizing trial positions in PCA space, severely impaired the decodability of stimulus features, demonstrating that orthogonal representations are critical for maintaining feature separability. These findings suggest that V1 population responses follow an orthogonal encoding geometry, and that population codes, rather than spatial maps, better capture feature representation. This principle may also serve as an important benchmark for V1-inspired deep neural networks.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"258 ","pages":"Article 102874"},"PeriodicalIF":6.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889916","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":"Prefrontal cortex interneurons and their contributions to attention, working memory, and adaptive behavior","authors":"Kianoush Banaie Boroujeni ,&nbsp;Pooja Balaram ,&nbsp;Paul Tiesinga ,&nbsp;Thilo Womelsdorf","doi":"10.1016/j.pneurobio.2025.102873","DOIUrl":"10.1016/j.pneurobio.2025.102873","url":null,"abstract":"<div><div>Inhibitory interneurons play central roles in regulating the input and output of cortical circuits, which in prefrontal cortices (PFC) subserve attention control, working memory and adaptive behavior. Understanding how interneurons support these higher order cognitive functions is a key question in a growing number of studies. Here, we delineate recent progress by surveying molecular, functional and computational motifs of interneurons in the prefrontal cortex of nonhuman primates and rodents. Among multiple transcriptomic and molecular subtypes of neurons several electrophysiologically identified <em>'eType'</em> interneurons are recruited during attention, learning, and working memory tasks. In nonhuman primate PFC, <em>eType</em> neurons with an inhibitory effect on the local circuit encode behaviorally relevant cues, unexpected outcomes, and tune working memory representations. These response profiles are consistent with the functional specializations proposed for PV+ , SST+ and VIP+ interneurons in rodents, which are recruited during attention and memory-guided tasks. We survey how these functional studies of interneuron types are supported by newly developed molecular and analytical tools and guided by computational studies that suggest unique circuit motifs for distinct types of interneurons to flexibly route synaptic inputs, compute prediction errors, and facilitate information retention in working memory.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"258 ","pages":"Article 102873"},"PeriodicalIF":6.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889898","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":"Molecular mechanisms of age-related vulnerability to traumatic brain injury","authors":"Pallavi Joshi ,&nbsp;Raghu Vemuganti","doi":"10.1016/j.pneurobio.2026.102890","DOIUrl":"10.1016/j.pneurobio.2026.102890","url":null,"abstract":"<div><div>Aging is associated with increased vulnerability to a wide variety of diseases and conditions, including traumatic brain injury (TBI). While advanced age is a known predictor of poorer outcomes following TBI, the molecular mechanisms underlying this susceptibility haven’t been completely characterized. This review discusses some of the primary pathways and physiological changes that are affected by aging and how they influence the post-TBI recovery in both experimental and clinical settings. Some of the age-related alterations implicated in geriatric TBI include loss of white matter, compromised blood-brain-barrier integrity, aggravated oxidative stress, mitochondrial dysfunction, higher cell death and synapse loss, increased and more prolonged neuroinflammation, compromised neural repair mechanisms, dysregulated proteasomal degradation leading to misfolded protein aggregation, and systemic changes such as peripheral organ dysfunction. This review further focuses on how the underlying molecular mechanisms involved in these changes influence long-term functional and behavioral outcomes after TBI. Lastly, some of the current and potential therapeutic interventions for geriatric TBI have also been discussed.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"258 ","pages":"Article 102890"},"PeriodicalIF":6.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097185","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":"Mixed-selective organization of reach and grasp in the primate fronto-parietal network","authors":"Alireza Fathian ,&nbsp;Sebastian J. Lehmann ,&nbsp;Jonathan A. Michaels ,&nbsp;Hansjörg Scherberger","doi":"10.1016/j.pneurobio.2026.102889","DOIUrl":"10.1016/j.pneurobio.2026.102889","url":null,"abstract":"<div><div>Reaching and grasping in primates require coordinated control of several parameters, such as grip type, wrist orientation, spatial position, and hand laterality. The anterior intraparietal (AIP) and rostral ventral premotor (F5) areas are key hubs in this process. This study used electrophysiological data to investigate how these parameters are co-represented in AIP and F5. The results indicate that neurons predominantly show mixed selectivity with stable temporal organization related to movement and pre-movement phases. This uncategorizable mixture of selectivity allows flexible decoding. Despite condition-dependent shifts, selectivity preferences were largely preserved across task conditions. Notably, object-related factors (orientation and position) remained more stable during grip type changes in AIP, whereas grip type was more stable in F5, suggesting a functional hierarchical organization of context-dependent coding in both areas. Together, despite the continuous range of mixed selectivity at the single-neuron level, neural ensembles exhibit a stable organization on the temporal and functional scales, enabling flexible readouts.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"258 ","pages":"Article 102889"},"PeriodicalIF":6.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097148","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":"NLRP3-mediated neuroinflammation in the ventrolateral orbital cortex contributes to the formation of morphine-induced addiction memory by upregulating GRIN3B","authors":"Yuan Liu ,&nbsp;Hongyun Chen ,&nbsp;Yaxin Guo ,&nbsp;Lijie Zhu ,&nbsp;Wenjing Meng ,&nbsp;Wenge Jia ,&nbsp;Chenchen Li ,&nbsp;Danya Zhou ,&nbsp;Wanyu Tu ,&nbsp;Tengteng Zhang ,&nbsp;Shanyong Yi ,&nbsp;Zhijun Yao ,&nbsp;Ben Liu ,&nbsp;Chuansheng Wang ,&nbsp;Ruiling Zhang ,&nbsp;Bin Zhao ,&nbsp;Lai Wei","doi":"10.1016/j.pneurobio.2025.102871","DOIUrl":"10.1016/j.pneurobio.2025.102871","url":null,"abstract":"<div><div>Addiction is a prevalent adverse effect of opioid analgesics. Morphine, a frequently employed opioid analgesic in clinical practice, has been demonstrated to possess rewarding properties that contribute to the establishment of addiction memory. Morphine administration elicits the NOD-like receptor protein 3 (NLRP3)-mediated neuroinflammatory response. Neuroinflammation can modulate the expression of GRIN/NMDAR (glutamate ionotropic receptor NMDA type), a key determinant of synaptic plasticity and memory formation. For this reason, we performed morphine conditioned place preference test to observe the effects of behavioral training, inhibition of NLRP3, and <em>Grin3b</em> knockout on the formation of addiction memory. Repeated morphine administration caused NLRP3-relative neuroinflammation, increased GRIN3B protein expression, and contributed to the formation of addiction memory in a task-dependent manner. Inhibiting NLRP3 attenuated neuroinflammation, decreased astrocyte activation and GRIN3B levels, and inhibited the formation of morphine-induced addiction memory by altering synaptic structure. Knocking out <em>Grin3b</em> impeded the formation of addiction memory but did not alleviate neuroinflammation or glial cells activation. Our findings indicate that NLRP3-mediated neuroinflammation modulates synaptic plasticity and contributes to the formation of morphine-induced addiction memory through GRIN3B.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"257 ","pages":"Article 102871"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769010","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":"Place field dynamics in retrosplenial cortex compared to hippocampus","authors":"Zaneta Navratilova ,&nbsp;Dhruba Banerjee ,&nbsp;Fjolla Muqolli ,&nbsp;Jordan Zhang ,&nbsp;Sunil P. Gandhi ,&nbsp;Bruce L. McNaughton","doi":"10.1016/j.pneurobio.2025.102867","DOIUrl":"10.1016/j.pneurobio.2025.102867","url":null,"abstract":"<div><div>The encoding, storage, and updating of memories in cortical networks are poorly understood. In retrosplenial cortex (RSC), cells respond to the animal’s position as it traverses a real or virtual (VR) linear track. Most position correlated cells (PCCs) in RSC require an intact hippocampus to form, but survive subsequent hippocampal damage. To examine whether RSC and hippocampal PCCs undergo remapping and spatial tuning development in parallel or sequentially, neuronal activity in RSC or CA1 was recorded using two-photon calcium imaging in mice running on VR tracks. RSC PCC activity underwent global remapping like CA1, with approximately the same dynamics of tuning development in the novel context. However, fields in RSC did not show place field expansion, in familiar or novel environments. Thus, while most properties of global remapping are shared between RSC and CA1, place field shift and expansion are notably restricted to hippocampus. Thus, our data suggests that RSC place specificity is either not ‘inherited’ directly from hippocampus or the hippocampal influence on RSC PCC formation may be restricted to hippocampal spikes occurring in the early phase of the theta rhythm (and thus late within the place field).</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"257 ","pages":"Article 102867"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744018","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":"Extracellular vesicle dysfunction contributes to synaptic and cognitive deficits in a mouse model of Angelman syndrome","authors":"Eduardo Penna ,&nbsp;Wenyue Su ,&nbsp;Tristan Reece ,&nbsp;Melissa Braga ,&nbsp;Hanna Shigemitsu ,&nbsp;Katelyn Ta ,&nbsp;Michel Baudry ,&nbsp;Xiaoning Bi","doi":"10.1016/j.pneurobio.2025.102870","DOIUrl":"10.1016/j.pneurobio.2025.102870","url":null,"abstract":"<div><div>Angelman syndrome (AS) is a devastating neurodevelopmental disorder caused by deficiency of the maternally inherited UBE3A. It is characterized by severe cognitive impairment, motor dysfunction, seizures, and developmental delays. Several mouse models of AS reproduce these debilitating features, including impaired memory function and synaptic plasticity, reduced dendritic spine density, and lysosomal alterations. Emerging research highlights the critical role of extracellular vesicles (EVs) in brain development and function, with growing evidence linking EV dysregulation to various neurological disorders. In this study, we first compared key features of EVs between wild-type (WT) and AS mice. EV secretion from forebrain synaptosomes was impaired in AS mice as compared to WT. Importantly, Ube3a was detected in EVs released from WT forebrain synaptosomes, suggesting a role for Ube3a in neuronal communication. We then identified TRPML1, a lysosomal ion channel, as a regulator of EV release and uptake, unveiling a novel molecular mechanism underlying EV dynamics. Furthermore, treatment with WT neuron-derived EVs significantly improved dendritic and spine morphology of cultured hippocampal neurons prepared from AS mice. Remarkably, systemic administration of WT brain-derived EVs restored hippocampal neuronal morphology and improved learning and memory in AS mice. These findings not only enhance our understanding of AS pathophysiology but also support EVs as a promising strategy for treating this currently incurable disorder.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"257 ","pages":"Article 102870"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775465","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":"Developmental embedding of parvalbumin-positive interneurons drives local and crosshemispheric prefrontal gamma synchrony","authors":"Anton Offermanns,&nbsp;Jastyn A. Pöpplau ,&nbsp;Ileana L. Hanganu-Opatz","doi":"10.1016/j.pneurobio.2025.102866","DOIUrl":"10.1016/j.pneurobio.2025.102866","url":null,"abstract":"<div><div>Gamma oscillations are critical for cortical cognitive processing. The ability to generate gamma oscillations evolves with age and requires cellular adjustments of the underlying neural networks. In the prefrontal cortex, gamma oscillations emerge relatively late compared to other cortical areas and the developmental mechanisms underlying the generation of adult-like gamma oscillations are poorly understood. Here, we combine <em>in vivo</em> electrophysiology and selective optogenetic manipulations of parvalbumin- (PV⁺) and somatostatin-positive (SOM⁺) interneurons in the mouse medial prefrontal cortex of both hemispheres along development to investigate their role for the age-dependent maturation of gamma oscillations. We show that crosshemispheric gamma synchrony strengthens with age, in line with the previously reported increase in local gamma power. The inhibitory effect of PV⁺ interneurons follows a similar timeline, enabling them to functionally operate within the classical gamma frequency range from adolescence onwards. In contrast, SOM⁺ interneurons have an age-independent inhibitory function, modulating beta-band oscillatory activity along development. These data identify the SOM⁺ to PV⁺ interneuron shift as a mechanism of gamma ontogeny and emergence of crosshemispheric synchrony in the developing prefrontal cortex.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"257 ","pages":"Article 102866"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705564","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 YAP/SCAP/SREBP1 pathway in astrocytes: A novel target for treating neonatal hypoxic-ischemic encephalopathy","authors":"Jiaojiao Wang ,&nbsp;Chunfang Dai ,&nbsp;Hao Yuan ,&nbsp;Qiuyun Tian ,&nbsp;Qian Xiao ,&nbsp;Xiaohuan Li ,&nbsp;Xiuyu Shi ,&nbsp;Zhifang Dong","doi":"10.1016/j.pneurobio.2025.102869","DOIUrl":"10.1016/j.pneurobio.2025.102869","url":null,"abstract":"<div><div>Astrocytes play a significant role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE), contributing to neuroexcitotoxicity and inflammatory responses. However, the specific pathways through which astrocytes influence neurons remain incompletely understood. In this study, we found that Yes-associated protein (YAP) was down-regulated and inactivated in hippocampal astrocytes in a hypoxic-ischemic brain damage (HIBD) rat model, as well as in astrocytes subjected to oxygen-glucose deprivation (OGD). Overexpression of YAP in astrocytes reduced neuronal death and improved motor, learning and memory dysfunction deficits associated with HIE. Further investigation demonstrated that YAP exerts neuroprotective effects by modulating lipid metabolism through the SCAP/SREBP1 pathway. Ultimately, activating YAP signaling by XMU-MP-1, a Hippo kinase MST1/2 inhibitor, partially restored brain tissue integrity and function, as well as improved motor, learning and memory functions in HIBD rats. In conclusion, our study has identified a novel YAP/SCAP/SREBP1 pathway that plays neuroprotective roles in HIE.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"257 ","pages":"Article 102869"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752067","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":"Divergence of cortical neurophysiology across different neurodegenerative disorders compared to healthy ageing","authors":"Michael Trubshaw ,&nbsp;Oliver Kohl ,&nbsp;Chetan Gohil ,&nbsp;Mats W.J. van Es ,&nbsp;Andrew J. Quinn ,&nbsp;Katie Yoganathan ,&nbsp;Evan Edmond ,&nbsp;Malcolm Proudfoot ,&nbsp;Nahid Zokaei ,&nbsp;Vanessa Raymont ,&nbsp;Jemma Pitt ,&nbsp;Tony Thayanandan ,&nbsp;Alexander G. Thompson ,&nbsp;Kevin Talbot ,&nbsp;Michele T. Hu ,&nbsp;Marlou Nadine Perquin ,&nbsp;Ece Kocagoncu ,&nbsp;James B. Rowe ,&nbsp;Mark W. Woolrich ,&nbsp;Anna C. Nobre ,&nbsp;Martin R. Turner","doi":"10.1016/j.pneurobio.2025.102865","DOIUrl":"10.1016/j.pneurobio.2025.102865","url":null,"abstract":"<div><div>Neurodegenerative diseases involve disruption of healthy brain network communication occurring before the emergence of symptoms. Magnetoencephalography (MEG) is sensitive to the magnetic fields generated by cortical neuronal activity, and is the most spatio-temporally accurate method of directly assessing neuronal activity non-invasively. We used MEG to directly compare three neurodegenerative disorders with a large healthy cohort to characterise patterns of activity deviating from healthy ageing.</div><div>Task-free MEG recordings were acquired from patients with Alzheimer’s disease (AD, n = 29), Parkinson’s disease (PD, n = 25), amyotrophic lateral sclerosis (ALS, n = 33) and healthy controls (HC, n = 191). Healthy ageing trajectories for metrics including spectral power (local neuronal recruitment), connectivity (long-range communication), 1/f exponent (power spectrum slope, which may reflect inhibition), and oscillatory speed were extracted. These metrics were compared pairwise between HC and patient groups, controlling for age and sex.</div><div>The modelled trajectories of healthy ageing included increasing beta power and oscillatory speed, with reduced power spectrum slope. PD, AD, and ALS groups all showed reductions in beta power and slowing of oscillatory activity compared to matched HC. In AD, older patients showed lower beta power compared with younger patients. Compared with matched HC, the power spectrum slope was uniquely reduced in ALS, in contrast to the increase seen in PD and AD. Gamma connectivity increased in AD and ALS.</div><div>MEG has unique potential as a source of biomarkers that might be used to detect deviation from healthy ageing if applied at an earlier presymptomatic stage of neurodegeneration than current tools permit. It might also provide outcome measures for prevention trials.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"257 ","pages":"Article 102865"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687957","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}