Progress in Neurobiology最新文献

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Mnemonically modulated perceptual processing to represent allocentric space in macaque inferotemporal cortex 猕猴颞下部皮层的记忆调节知觉处理,以表示分配中心空间。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-10-01 DOI: 10.1016/j.pneurobio.2024.102670
Ao Li , He Chen , Yuji Naya
{"title":"Mnemonically modulated perceptual processing to represent allocentric space in macaque inferotemporal cortex","authors":"Ao Li ,&nbsp;He Chen ,&nbsp;Yuji Naya","doi":"10.1016/j.pneurobio.2024.102670","DOIUrl":"10.1016/j.pneurobio.2024.102670","url":null,"abstract":"<div><div>To encode allocentric space information of a viewing object, it is important to relate perceptual information in the first-person perspective to the representation of an entire scene which would be constructed before. A substantial number of studies investigated the constructed scene information (e.g., cognitive map). However, only few studies have focused on its influence on perceptual processing. Therefore, we designed a visually guided saccade task requiring monkeys to gaze at objects in different locations on different backgrounds clipped from large self-designed mosaic pictures (parental pictures). In each trial, we presented moving backgrounds prior to object presentations, indicating a frame position of the background image on a parental picture. We recorded single-unit activities from 377 neurons in the posterior inferotemporal (PIT) cortex of two macaques. Equivalent numbers of neurons showed space-related (119 of 377) and object-related (125 of 377) information. The space-related neurons coded the gaze locations and background images jointly rather than separately. These results suggest that PIT neurons represent a particular location within a particular background image. Interestingly, frame positions of background images on parental pictures modulated the space-related responses dependently on parental pictures. As the frame positions could be acquired by only preceding visual experiences, the present results may provide neuronal evidence of a mnemonic effect on current perception, which might represent allocentric object location in a scene beyond the current view.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102670"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375877","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
Corrigendum to “Adiponectin ameliorates hypoperfusive cognitive deficits by boosting a neuroprotective microglial response” [Prog. Neurobiol. 205 (2021) 102125] 对 "脂肪连通素通过增强神经保护性微胶质细胞反应改善低通透性认知障碍 "的更正 [Prog. Neurobiol. 205 (2021) 102125]
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-10-01 DOI: 10.1016/j.pneurobio.2024.102631
{"title":"Corrigendum to “Adiponectin ameliorates hypoperfusive cognitive deficits by boosting a neuroprotective microglial response” [Prog. Neurobiol. 205 (2021) 102125]","authors":"","doi":"10.1016/j.pneurobio.2024.102631","DOIUrl":"10.1016/j.pneurobio.2024.102631","url":null,"abstract":"","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102631"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098230","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
Distinct 5-HT receptor subtypes regulate claustrum excitability by serotonin and the psychedelic, DOI 不同的 5-HT 受体亚型受血清素和迷幻药的影响而调节视网膜的兴奋性,DOI.
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-09-01 DOI: 10.1016/j.pneurobio.2024.102660
Tanner L. Anderson , Jack V. Keady , Judy Songrady , Navid S. Tavakoli , Artin Asadipooya , Ryson E. Neeley , Jill R. Turner , Pavel I. Ortinski
{"title":"Distinct 5-HT receptor subtypes regulate claustrum excitability by serotonin and the psychedelic, DOI","authors":"Tanner L. Anderson ,&nbsp;Jack V. Keady ,&nbsp;Judy Songrady ,&nbsp;Navid S. Tavakoli ,&nbsp;Artin Asadipooya ,&nbsp;Ryson E. Neeley ,&nbsp;Jill R. Turner ,&nbsp;Pavel I. Ortinski","doi":"10.1016/j.pneurobio.2024.102660","DOIUrl":"10.1016/j.pneurobio.2024.102660","url":null,"abstract":"<div><p>Recent evidence indicates that neuronal activity within the claustrum (CLA) may be central to cellular and behavioral responses to psychedelic hallucinogens. The CLA prominently innervates many cortical targets and displays exceptionally high levels of serotonin (5-HT) binding. However, the influence of serotonin receptors, prime targets of psychedelic drug action, on CLA activity remains unexplored. We characterize the CLA expression of all known 5-HT subtypes and contrast the effects of 5-HT and the psychedelic hallucinogen, 2,5-dimethoxy-4-iodoamphetamine (DOI), on excitability of cortical-projecting CLA neurons. We find that the CLA is particularly enriched with 5-HT2C receptors, expressed predominantly on glutamatergic neurons. Electrophysiological recordings from CLA neurons that project to the anterior cingulate cortex (ACC) indicate that application of 5-HT inhibits glutamate receptor-mediated excitatory postsynaptic currents (EPSCs). In contrast, application of DOI stimulates EPSCs. We find that the opposite effects of 5-HT and DOI on synaptic signaling can both be reversed by inhibition of the 5-HT2C, but not 5-HT2A, receptors. We identify specific 5-HT receptor subtypes as serotonergic regulators of the CLA excitability and argue against the canonical role of 5-HT2A in glutamatergic synapse response to psychedelics within the CLA-ACC circuit.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102660"},"PeriodicalIF":6.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111393","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
Naturalistic movies and encoding analysis define areal borders in marmoset third-tier visual cortex 自然电影和编码,分析狨猴第三层视觉皮层中的区域边界定义。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-08-03 DOI: 10.1016/j.pneurobio.2024.102657
Daisuke Shimaoka , Yan Tat Wong , Marcello G.P. Rosa , Nicholas Seow Chiang Price
{"title":"Naturalistic movies and encoding analysis define areal borders in marmoset third-tier visual cortex","authors":"Daisuke Shimaoka ,&nbsp;Yan Tat Wong ,&nbsp;Marcello G.P. Rosa ,&nbsp;Nicholas Seow Chiang Price","doi":"10.1016/j.pneurobio.2024.102657","DOIUrl":"10.1016/j.pneurobio.2024.102657","url":null,"abstract":"<div><p>Accurate definition of the borders of cortical visual areas is essential for the study of neuronal processes leading to perception. However, data used for definition of areal boundaries have suffered from issues related to resolution, uniform coverage, or suitability for objective analysis, leading to ambiguity. Here, we present a novel approach that combines widefield optical imaging, presentation of naturalistic movies, and encoding model analysis, to objectively define borders in the primate extrastriate cortex. We applied this method to test conflicting hypotheses about the third-tier visual cortex, where areal boundaries have remained controversial. We demonstrate pronounced tuning preferences in the third-tier areas, and an organizational structure in which the dorsomedial area (DM) contains representations of both the upper and lower contralateral quadrants, and is located immediate anterior to V2. High-density electrophysiological recordings with a Neuropixels probe confirm these findings. Our encoding-model approach offers a powerful, objective way to disambiguate areal boundaries.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102657"},"PeriodicalIF":6.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000935/pdfft?md5=bc7941c87bc2ead50297eb74962e4f67&pid=1-s2.0-S0301008224000935-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894177","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
A free intravesicular C-terminal of otoferlin is essential for synaptic vesicle docking and fusion at auditory inner hair cell ribbon synapses 听觉内毛细胞带状突触的突触囊泡对接和融合离不开自由的囊泡内C端奥托费林。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-08-03 DOI: 10.1016/j.pneurobio.2024.102658
Didier Dulon , Jacques Boutet de Monvel , Baptiste Plion , Adeline Mallet , Christine Petit , Steven Condamine , Yohan Bouleau , Saaid Safieddine
{"title":"A free intravesicular C-terminal of otoferlin is essential for synaptic vesicle docking and fusion at auditory inner hair cell ribbon synapses","authors":"Didier Dulon ,&nbsp;Jacques Boutet de Monvel ,&nbsp;Baptiste Plion ,&nbsp;Adeline Mallet ,&nbsp;Christine Petit ,&nbsp;Steven Condamine ,&nbsp;Yohan Bouleau ,&nbsp;Saaid Safieddine","doi":"10.1016/j.pneurobio.2024.102658","DOIUrl":"10.1016/j.pneurobio.2024.102658","url":null,"abstract":"<div><p>Our understanding of how otoferlin, the major calcium sensor in inner hair cells (IHCs) synaptic transmission, contributes to the overall dynamics of synaptic vesicle (SV) trafficking remains limited. To address this question, we generated a knock-in mouse model expressing an otoferlin-GFP protein, where GFP was fused to its C-terminal transmembrane domain. Similar to the wild type protein, the GFP-tagged otoferlin showed normal expression and was associated with IHC SV. Surprisingly, while the heterozygote <em>Otof</em> <sup><em>+/GFP</em></sup> mice exhibited a normal hearing function, homozygote <em>Otof</em> <sup><em>GFP/GFP</em></sup> mice were profoundly deaf attributed to severe reduction in SV exocytosis. Fluorescence recovery after photobleaching revealed a markedly increased mobile fraction of the otof-GFP-associated SV in <em>Otof <sup>GFP/GFP</sup></em> IHCs. Correspondingly, 3D-electron tomographic of the ribbon synapses indicated a reduced density of SV attached to the ribbon active zone. Collectively, these results indicate that otoferlin requires a free intravesicular C-terminal end for normal SV docking and fusion.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102658"},"PeriodicalIF":6.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000947/pdfft?md5=61dac4df5fe8a53220a48368fcbaa2d7&pid=1-s2.0-S0301008224000947-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894176","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
Orientation selectivity mapping in the visual cortex 视觉皮层的方向选择性映射。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-07-14 DOI: 10.1016/j.pneurobio.2024.102656
Mei-Lan Liu , Yi-Peng Liu , Xin-Xia Guo , Zhi-Yi Wu , Xiao-Tong Zhang , Anna Wang Roe , Jia-Ming Hu
{"title":"Orientation selectivity mapping in the visual cortex","authors":"Mei-Lan Liu ,&nbsp;Yi-Peng Liu ,&nbsp;Xin-Xia Guo ,&nbsp;Zhi-Yi Wu ,&nbsp;Xiao-Tong Zhang ,&nbsp;Anna Wang Roe ,&nbsp;Jia-Ming Hu","doi":"10.1016/j.pneurobio.2024.102656","DOIUrl":"10.1016/j.pneurobio.2024.102656","url":null,"abstract":"<div><p>The orientation map is one of the most well-studied functional maps of the visual cortex. However, results from the literature are of different qualities. Clear boundaries among different orientation domains and blurred uncertain distinctions were shown in different studies. These unclear imaging results will lead to an inaccuracy in depicting cortical structures, and the lack of consideration in experimental design will also lead to biased depictions of the cortical features. How we accurately define orientation domains will impact the entire field of research. In this study, we test how spatial frequency (SF), stimulus size, location, chromatic, and data processing methods affect the orientation functional maps (including a large area of dorsal V4, and parts of dorsal V1) acquired by intrinsic signal optical imaging. Our results indicate that, for large imaging fields, large grating stimuli with mixed SF components should be considered to acquire the orientation map. A diffusion model image enhancement based on the difference map could further improve the map quality. In addition, the similar outcomes of achromatic and chromatic gratings indicate two alternative types of afferents from LGN, pooling in V1 to generate cue-invariant orientation selectivity.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102656"},"PeriodicalIF":6.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000923/pdfft?md5=d10cbf14051a20a184842cf64d84b05b&pid=1-s2.0-S0301008224000923-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620760","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
Population coding for figure-ground texture segregation in macaque V1 and V4 猕猴 V1 和 V4 中图形-地面纹理分离的群体编码。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-07-04 DOI: 10.1016/j.pneurobio.2024.102655
Xing-Nan Zhao , Xing-Si Dong , Dan-Qing Jiang , Si Wu , Shi-Ming Tang , Cong Yu
{"title":"Population coding for figure-ground texture segregation in macaque V1 and V4","authors":"Xing-Nan Zhao ,&nbsp;Xing-Si Dong ,&nbsp;Dan-Qing Jiang ,&nbsp;Si Wu ,&nbsp;Shi-Ming Tang ,&nbsp;Cong Yu","doi":"10.1016/j.pneurobio.2024.102655","DOIUrl":"10.1016/j.pneurobio.2024.102655","url":null,"abstract":"<div><p>Object recognition often involves the brain segregating objects from their surroundings. Neurophysiological studies of figure-ground texture segregation have yielded inconsistent results, particularly on whether V1 neurons can perform figure-ground texture segregation or just detect texture borders. To address this issue from a population perspective, we utilized two-photon calcium imaging to simultaneously record the responses of large samples of V1 and V4 neurons to figure-ground texture stimuli in awake, fixating macaques. The average response changes indicate that V1 neurons mainly detect texture borders, while V4 neurons are involved in figure-ground segregation. However, population analysis (SVM decoding of PCA-transformed neuronal responses) reveal that V1 neurons not only detect figure-ground borders, but also contribute to figure-ground texture segregation, although requiring substantially more principal components than V4 neurons to reach a 75 % decoding accuracy. Individually, V1/V4 neurons showing larger (negative/positive) figure-ground response differences contribute more to figure-ground segregation. But for V1 neurons, the contribution becomes significant only when many principal components are considered. We conclude that V1 neurons participate in figure-ground segregation primarily by defining the figure borders, and the poorly structured figure-ground information V1 neurons carry could be further utilized by V4 neurons to accomplish figure-ground segregation.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102655"},"PeriodicalIF":6.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538570","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
The homogenous hippocampus: How hippocampal cells process available and potential goals 同质海马:海马细胞如何处理可用目标和潜在目标。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-07-02 DOI: 10.1016/j.pneurobio.2024.102653
Neil McNaughton , David Bannerman
{"title":"The homogenous hippocampus: How hippocampal cells process available and potential goals","authors":"Neil McNaughton ,&nbsp;David Bannerman","doi":"10.1016/j.pneurobio.2024.102653","DOIUrl":"10.1016/j.pneurobio.2024.102653","url":null,"abstract":"<div><p>We present here a view of the firing patterns of hippocampal cells that is contrary, both functionally and anatomically, to conventional wisdom. We argue that the hippocampus responds to efference copies of goals encoded elsewhere; and that it uses these to detect and resolve conflict or interference between goals in general. While goals can involve space, hippocampal cells do not encode spatial (or other special types of) memory, as such. We also argue that the transverse circuits of the hippocampus operate in an essentially homogeneous way along its length. The apparently different functions of different parts (e.g. memory retrieval versus anxiety) result from the different (situational/motivational) inputs on which those parts perform the same fundamental computational operations. On this view, the key role of the hippocampus is the iterative adjustment, via Papez-like circuits, of synaptic weights in cell assemblies elsewhere.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102653"},"PeriodicalIF":6.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000893/pdfft?md5=65565ae54d4a1c6567131ef55d7dc0d0&pid=1-s2.0-S0301008224000893-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498768","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
Adolescent cannabinoid exposure rescues phencyclidine-induced social deficits through modulation of CA2 transmission 青春期大麻素暴露可通过调节 CA2 传输来挽救苯环利定诱发的社交障碍。
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-06-30 DOI: 10.1016/j.pneurobio.2024.102652
Marta Barrera-Conde , Carla Ramon-Duaso , Jose Antonio González-Parra , Emma Veza-Estevez , Vivien Chevaleyre , Rebecca A. Piskorowski , Rafael de la Torre , Arnau Busquets-García , Patricia Robledo
{"title":"Adolescent cannabinoid exposure rescues phencyclidine-induced social deficits through modulation of CA2 transmission","authors":"Marta Barrera-Conde ,&nbsp;Carla Ramon-Duaso ,&nbsp;Jose Antonio González-Parra ,&nbsp;Emma Veza-Estevez ,&nbsp;Vivien Chevaleyre ,&nbsp;Rebecca A. Piskorowski ,&nbsp;Rafael de la Torre ,&nbsp;Arnau Busquets-García ,&nbsp;Patricia Robledo","doi":"10.1016/j.pneurobio.2024.102652","DOIUrl":"10.1016/j.pneurobio.2024.102652","url":null,"abstract":"<div><p>Psychotic disorders entail intricate conditions marked by disruptions in cognition, perception, emotions, and social behavior. Notably, psychotic patients who use cannabis tend to show less severe deficits in social behaviors, such as the misinterpretation of social cues and the inability to interact with others. However, the biological underpinnings of this epidemiological interaction remain unclear. Here, we used the NMDA receptor blocker phencyclidine (PCP) to induce psychotic-like states and to study the impact of adolescent cannabinoid exposure on social behavior deficits and synaptic transmission changes in hippocampal area CA2, a region known to be active during social interactions. In particular, adolescent mice underwent 7 days of subchronic treatment with the synthetic cannabinoid, WIN 55, 212–2 (WIN) followed by one injection of PCP. Using behavioral, biochemical, and electrophysiological approaches, we showed that PCP persistently reduced sociability, decreased GAD67 expression in the hippocampus, and induced GABAergic deficits in proximal inputs from CA3 and distal inputs from the entorhinal cortex (EC) to CA2. Notably, WIN exposure during adolescence specifically restores adult sociability deficits, the expression changes in GAD67, and the GABAergic impairments in the EC-CA2 circuit, but not in the CA3-CA2 circuit. Using a chemogenetic approach to target EC-CA2 projections, we demonstrated the involvement of this specific circuit on sociability deficits. Indeed, enhancing EC-CA2 transmission was sufficient to induce sociability deficits in vehicle-treated mice, but not in animals treated with WIN during adolescence, suggesting a mechanism by which adolescent cannabinoid exposure rescues sociability deficits caused by enhanced EC-CA2 activity in adult mice.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102652"},"PeriodicalIF":6.7,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493202","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
Astrocyte-secreted C3 signaling impairs neuronal development and cognition in autoimmune diseases 星形胶质细胞分泌的C3信号损害自身免疫性疾病的神经元发育和认知能力
IF 6.7 2区 医学
Progress in Neurobiology Pub Date : 2024-06-28 DOI: 10.1016/j.pneurobio.2024.102654
Fan Zhu , Pengyan He , Wei Jiang , Shabbir Khan Afridi , Huiming Xu , Maali Alahmad , Yu-Wen Alvin Huang , Wei Qiu , Guangyou Wang , Changyong Tang
{"title":"Astrocyte-secreted C3 signaling impairs neuronal development and cognition in autoimmune diseases","authors":"Fan Zhu ,&nbsp;Pengyan He ,&nbsp;Wei Jiang ,&nbsp;Shabbir Khan Afridi ,&nbsp;Huiming Xu ,&nbsp;Maali Alahmad ,&nbsp;Yu-Wen Alvin Huang ,&nbsp;Wei Qiu ,&nbsp;Guangyou Wang ,&nbsp;Changyong Tang","doi":"10.1016/j.pneurobio.2024.102654","DOIUrl":"10.1016/j.pneurobio.2024.102654","url":null,"abstract":"<div><p>Neuromyelitis optica (NMO) arises from primary astrocytopathy induced by autoantibodies targeting the astroglial protein aquaporin 4 (AQP4), leading to severe neurological sequelae such as vision loss, motor deficits, and cognitive decline. Mounting evidence has shown that dysregulated activation of complement components contributes to NMO pathogenesis. Complement C3 deficiency has been shown to protect against hippocampal neurodegeneration and cognitive decline in neurodegenerative disorders (e.g., Alzheimer's disease, AD) and autoimmune diseases (e.g., multiple sclerosis, MS). However, whether inhibiting the C3 signaling can ameliorate cognitive dysfunctions in NMO remains unclear. In this study, we found that the levels of C3a, a split product of C3, significantly correlate with cognitive impairment in our patient cohort. In response to the stimulation of AQP4 autoantibodies, astrocytes were activated to secrete complement C3, which inhibited the development of cultured neuronal dendritic arborization. NMO mouse models exhibited reduced adult hippocampal newborn neuronal dendritic and spine development, as well as impaired learning and memory functions, which could be rescued by decreasing C3 levels in astrocytes. Mechanistically, we found that C3a engaged with C3aR to impair neuronal development by dampening β-catenin signalling. Additionally, inhibition of the C3-C3aR-GSK3β/β-catenin cascade restored neuronal development and ameliorated cognitive impairments. Collectively, our results suggest a pivotal role of the activation of the C3-C3aR network in neuronal development and cognition through mediating astrocyte and adult-born neuron communication, which represents a potential therapeutic target for autoimmune-related cognitive impairment diseases.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102654"},"PeriodicalIF":6.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470452","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
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