bioRxiv : the preprint server for biology最新文献_第10页

Altered primary somatosensory neuron development in a Pten heterozygous model for autism spectrum disorder. Pten对DRG感觉神经元多样化的内在控制。

bioRxiv : the preprint server for biology Pub Date : 2025-01-17 DOI: 10.1101/2023.08.04.552039

Alejandra Fernandez, Nick Sarn, Charis Eng, Kevin M Wright

{"title":"Altered primary somatosensory neuron development in a Pten heterozygous model for autism spectrum disorder.","authors":"Alejandra Fernandez, Nick Sarn, Charis Eng, Kevin M Wright","doi":"10.1101/2023.08.04.552039","DOIUrl":"10.1101/2023.08.04.552039","url":null,"abstract":"Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interactions, repetitive behaviors, and hyper- or hyposensitivity to sensory stimuli. The mechanisms underlying the emergence of sensory features in ASD are not fully understood, but recent studies in rodent models highlight that these may result from differences in primary sensory neurons themselves. We examined sensory behaviors in a Pten haploinsufficient mouse model ( Pten Het ) for syndromic ASD and identified elevated responses to mechanical stimuli and a higher threshold to thermal responses. Transcriptomic and in vivo anatomical analysis identified alterations in subtype-specific markers of primary somatosensory neurons in Pten Het dorsal root ganglia (DRG). These defects emerge early during DRG development and involve dysregulation of multiple signaling pathways downstream of Pten . Finally, we show that mice harboring an ASD-associated mutation ( Pten Y69H ) also show altered expression of somatosensory neuron subtype-specific markers. Together, these results show that precise levels of Pten are required for proper somatosensory development and provide insight into the molecular and cellular basis of sensory abnormalities in a model for syndromic ASD.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient coding in biophysically realistic excitatory-inhibitory spiking networks. 高效兴奋-抑制尖峰网络的结构、动力学、编码和最佳生物物理参数。

bioRxiv : the preprint server for biology Pub Date : 2025-01-17 DOI: 10.1101/2024.04.24.590955

Veronika Koren, Simone Blanco Malerba, Tilo Schwalger, Stefano Panzeri

{"title":"Efficient coding in biophysically realistic excitatory-inhibitory spiking networks.","authors":"Veronika Koren, Simone Blanco Malerba, Tilo Schwalger, Stefano Panzeri","doi":"10.1101/2024.04.24.590955","DOIUrl":"10.1101/2024.04.24.590955","url":null,"abstract":"The principle of efficient coding posits that sensory cortical networks are designed to encode maximal sensory information with minimal metabolic cost. Despite the major influence of efficient coding in neuroscience, it has remained unclear whether fundamental empirical properties of neural network activity can be explained solely based on this normative principle. Here, we derive the structural, coding, and biophysical properties of excitatory-inhibitory recurrent networks of spiking neurons that emerge directly from imposing that the network minimizes an instantaneous loss function and a time-averaged performance measure enacting efficient coding. We assumed that the network encodes a number of independent stimulus features varying with a time scale equal to the membrane time constant of excitatory and inhibitory neurons. The optimal network has biologically-plausible biophysical features, including realistic integrate-and-fire spiking dynamics, spike-triggered adaptation, and a non-specific excitatory external input. The excitatory-inhibitory recurrent connectivity between neurons with similar stimulus tuning implements feature-specific competition, similar to that recently found in visual cortex. Networks with unstructured connectivity cannot reach comparable levels of coding efficiency. The optimal ratio of excitatory vs inhibitory neurons and the ratio of mean inhibitory-to-inhibitory vs excitatory-to-inhibitory connectivity are comparable to those of cortical sensory networks. The efficient network solution exhibits an instantaneous balance between excitation and inhibition. The network can perform efficient coding even when external stimuli vary over multiple time scales. Together, these results suggest that key properties of biological neural networks may be accounted for by efficient coding.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Contiguous and complete assemblies of Blastocystis gut microbiome-associated protists reveal evolutionary diversification to host ecology. 原生胚泡菌的杂交组合揭示了宿主生态的进化多样化。

bioRxiv : the preprint server for biology Pub Date : 2025-01-15 DOI: 10.1101/2023.11.20.567959

Abigail L Lind, Nathan A McDonald, Elias R Gerrick, Ami S Bhatt, Katherine S Pollard

{"title":"Contiguous and complete assemblies of Blastocystis gut microbiome-associated protists reveal evolutionary diversification to host ecology.","authors":"Abigail L Lind, Nathan A McDonald, Elias R Gerrick, Ami S Bhatt, Katherine S Pollard","doi":"10.1101/2023.11.20.567959","DOIUrl":"10.1101/2023.11.20.567959","url":null,"abstract":"Blastocystis, an obligate host-associated protist, is the most common microbial eukaryote in the human gut and is widely distributed across vertebrate hosts. The evolutionary transition of Blastocystis from its free-living stramenopile ancestors to a radiation of host-associated organisms is poorly understood. To explore this, we cultured and sequenced eight strains representing the significant phylogenetic diversity of the genus using long-read, short-read, and Hi-C DNA sequencing, alongside gene annotation and RNA sequencing. Comparative genomic analyses revealed significant variation in gene content and genome structure across Blastocystis. Notably, three strains from herbivorous tortoises, phylogenetically distant from human subtypes, have markedly larger genomes with longer introns and intergenic regions, and retain canonical stop codons absent in the human-associated strains. Despite these genetic differences, all eight isolates exhibit gene losses linked to the reduced cellular complexity of Blastocystis, including losses of cilia and flagella genes, microtubule motor genes, and signal transduction genes. Isolates from herbivorous tortoises contained higher numbers of plant carbohydrate-metabolizing enzymes, suggesting that like gut bacteria, these protists ferment plant material in the host gut. We find evidence that some of these carbohydrate-metabolizing enzymes were horizontally acquired from bacteria, indicating that horizontal gene transfer is an ongoing process in Blastocystis that has contributed to host-related adaptation. Together, these results highlight substantial genetic and metabolic diversity within the Blastocystis genus, indicating different lineages of Blastocystis have varied ecological roles in the host gut.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Narrow Range of Transcript-error Rates Across the Tree of Life. 生命之树转录错误率的狭窄范围。

bioRxiv : the preprint server for biology Pub Date : 2025-01-14 DOI: 10.1101/2023.05.02.538944

Weiyi Li, Stephan Baehr, Michelle Marasco, Lauren Reyes, Danielle Brister, Craig S Pikaard, Jean-Francois Gout, Marc Vermulst, Michael Lynch

{"title":"A Narrow Range of Transcript-error Rates Across the Tree of Life.","authors":"Weiyi Li, Stephan Baehr, Michelle Marasco, Lauren Reyes, Danielle Brister, Craig S Pikaard, Jean-Francois Gout, Marc Vermulst, Michael Lynch","doi":"10.1101/2023.05.02.538944","DOIUrl":"10.1101/2023.05.02.538944","url":null,"abstract":"The expression of genomically-encoded information is not error-free. Transcript-error rates are dramatically higher than DNA-level mutation rates, and despite their transient nature, the steady-state load of such errors must impose some burden on cellular performance. However, a broad perspective on the degree to which transcript-error rates are constrained by natural selection and diverge among lineages remains to be developed. Here, we present a genome-wide analysis of transcript-error rates across the Tree of Life using a modified rolling-circle sequencing method, revealing that the range in error rates is remarkably narrow across diverse species. Transcript errors tend to be randomly distributed, with little evidence supporting local control of error rates associated with gene-expression levels. A majority of transcript errors result in missense errors if translated, and as with a fraction of nonsense transcript errors, these are underrepresented relative to random expectations, suggesting the existence of mechanisms for purging some such errors. To quantitatively understand how natural selection and random genetic drift might shape transcript-error rates across species, we present a model based on cell biology and population genetics, incorporating information on cell volume, proteome size, average degree of exposure of individual errors, and effective population size. However, while this model provides a framework for understanding the evolution of this highly conserved trait, as currently structured it explains only 20% of the variation in the data, suggesting a need for further theoretical work in this area.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81289250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury. 骨膜骨骼干细胞可以迁移到骨髓中，并在受伤后支持造血。

bioRxiv : the preprint server for biology Pub Date : 2025-01-14 DOI: 10.1101/2023.01.12.523842

Tony Marchand, Kemi E Akinnola, Shoichiro Takeishi, Maria Maryanovich, Sandra Pinho, Julien Saint-Vanne, Alexander Birbrair, Thierry Lamy, Karin Tarte, Paul S Frenette, Kira Gritsman

{"title":"Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury.","authors":"Tony Marchand, Kemi E Akinnola, Shoichiro Takeishi, Maria Maryanovich, Sandra Pinho, Julien Saint-Vanne, Alexander Birbrair, Thierry Lamy, Karin Tarte, Paul S Frenette, Kira Gritsman","doi":"10.1101/2023.01.12.523842","DOIUrl":"10.1101/2023.01.12.523842","url":null,"abstract":"Skeletal stem cells have been isolated from various tissues, including periosteum and bone marrow, where they exhibit key functions in bone biology and hematopoiesis, respectively. The role of periosteal skeletal stem cells in bone regeneration and healing has been extensively studied, but their ability to contribute to the bone marrow stroma is still under debate. In the present study, we characterized a whole bone transplantation model that mimics the initial bone marrow necrosis and fatty infiltration seen after injury. Using this model and a lineage tracing approach, we observed the migration of periosteal skeletal stem cells into the bone marrow after transplantation. Once in the bone marrow, periosteal skeletal stem cells are phenotypically and functionally reprogrammed into bone marrow mesenchymal stem cells that express high levels of hematopoietic stem cell niche factors such as Cxcl12 and Kitl. In addition, using ex vivo and in vivo approaches, we found that periosteal skeletal stem cells are more resistant to acute stress than bone marrow mesenchymal stem cells. These results highlight the plasticity of periosteal skeletal stem cells and their potential role in bone marrow regeneration after bone marrow injury.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9333505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain using 7 Tesla fMRI. 人类大脑中同种异体间感受系统的皮层和皮层下映射：7特斯拉fMRI的复制和扩展。

bioRxiv : the preprint server for biology Pub Date : 2025-01-13 DOI: 10.1101/2023.07.20.548178

Jiahe Zhang, Danlei Chen, Philip Deming, Tara Srirangarajan, Jordan Theriault, Philip A Kragel, Ludger Hartley, Kent M Lee, Kieran McVeigh, Tor D Wager, Lawrence L Wald, Ajay B Satpute, Karen S Quigley, Susan Whitfield-Gabrieli, Lisa Feldman Barrett, Marta Bianciardi

{"title":"Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain using 7 Tesla fMRI.","authors":"Jiahe Zhang, Danlei Chen, Philip Deming, Tara Srirangarajan, Jordan Theriault, Philip A Kragel, Ludger Hartley, Kent M Lee, Kieran McVeigh, Tor D Wager, Lawrence L Wald, Ajay B Satpute, Karen S Quigley, Susan Whitfield-Gabrieli, Lisa Feldman Barrett, Marta Bianciardi","doi":"10.1101/2023.07.20.548178","DOIUrl":"10.1101/2023.07.20.548178","url":null,"abstract":"The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, called allostasis. In support of allostasis, the brain continually models the sensory state of the body, called interoception. We replicated and extended a large-scale system supporting allostasis and interoception in the human brain using ultra-high precision 7 Tesla functional magnetic resonance imaging (fMRI) (N = 90), improving the precision of subgenual and pregenual anterior cingulate topography combined with extensive brainstem nuclei mapping. We observed over 90% of the anatomical connections published in tract-tracing studies in non-human animals. The system also included regions of dense intrinsic connectivity broadly throughout the system, some of which were identified previously as part of the backbone of neural communication across the brain. These results strengthen previous evidence for a whole-brain system supporting the modeling and regulation of the internal milieu of the body.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/d3/nihpp-2023.07.20.548178v1.PMC10401932.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vectorized instructive signals in cortical dendrites during a brain-computer interface task. 脑机接口任务中皮质树突的矢量化指示信号。

bioRxiv : the preprint server for biology Pub Date : 2025-01-13 DOI: 10.1101/2023.11.03.565534

Valerio Francioni, Vincent D Tang, Enrique H S Toloza, Norma J Brown, Mark T Harnett

{"title":"Vectorized instructive signals in cortical dendrites during a brain-computer interface task.","authors":"Valerio Francioni, Vincent D Tang, Enrique H S Toloza, Norma J Brown, Mark T Harnett","doi":"10.1101/2023.11.03.565534","DOIUrl":"10.1101/2023.11.03.565534","url":null,"abstract":"Vectorization of teaching signals is a key element of virtually all modern machine learning algorithms, including backpropagation, target propagation and reinforcement learning. Vectorization allows a scalable and computationally efficient solution to the credit assignment problem by tailoring instructive signals to individual neurons. Recent theoretical models have suggested that neural circuits could implement single-phase vectorized learning at the cellular level by processing feedforward and feedback information streams in separate dendritic compartments1-5. This presents a compelling, but untested, hypothesis for how cortical circuits could solve credit assignment in the brain. We leveraged a neurofeedback brain-computer interface (BCI) task with an experimenter-defined reward function to test for vectorized instructive signals in dendrites. We trained mice to modulate the activity of two spatially intermingled populations (4 or 5 neurons each) of layer 5 pyramidal neurons in the retrosplenial cortex to rotate a visual grating towards a target orientation while we recorded GCaMP activity from somas and corresponding distal apical dendrites. We observed that the relative magnitudes of somatic versus dendritic signals could be predicted using the activity of the surrounding network and contained information about task-related variables that could serve as instructive signals, including reward and error. The signs of these putative teaching signals both depended on the causal role of individual neurons in the task and predicted changes in overall activity over the course of learning. Furthermore, targeted optogenetic perturbation of these signals disrupted learning. These results provide the first biological evidence of a vectorized instructive signal in the brain, implemented via semi-independent computation in cortical dendrites, unveiling a potential mechanism for solving credit assignment in the brain.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92158003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer's Disease. RNA G-四链体在衰老和阿尔茨海默病中的新作用。

bioRxiv : the preprint server for biology Pub Date : 2025-01-13 DOI: 10.1101/2023.10.02.560545

Lena Kallweit, Eric D Hamlett, Hannah Saternos, Anah Gilmore, Ann-Charlotte Granholm, Scott Horowitz

{"title":"Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer's Disease.","authors":"Lena Kallweit, Eric D Hamlett, Hannah Saternos, Anah Gilmore, Ann-Charlotte Granholm, Scott Horowitz","doi":"10.1101/2023.10.02.560545","DOIUrl":"10.1101/2023.10.02.560545","url":null,"abstract":"Introduction: As the world population ages, new molecular targets in aging and Alzheimer's Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored. METHODS: In this study, we examined human hippocampal postmortem tissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.Results: We found that rG4 immunostaining strongly increased in the hippocampus with both age and with AD severity. We further found that neurons with accumulation of phospho-tau immunostaining contained rG4s, that rG4 structure can drive tau aggregation, and that rG4 staining density depended on APOE genotype in the human tissue examined.Discussion: Combined with previous studies showing the dependence of rG4 structure on stress and the extreme power of rG4s at oligomerizing proteins, we propose a model of neurodegeneration in which chronic rG4 formation is linked to proteostasis collapse. These morphological findings suggest that further investigation of RNA structure in neurodegeneration is a critical avenue for future treatments and diagnoses.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592952/pdf/nihpp-2023.10.02.560545v1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease. 阿尔茨海默病神经元的蛋白稳态和溶酶体质量控制缺陷

bioRxiv : the preprint server for biology Pub Date : 2025-01-13 DOI: 10.1101/2023.03.27.534444

Ching-Chieh Chou, Ryan Vest, Miguel A Prado, Joshua Wilson-Grady, Joao A Paulo, Yohei Shibuya, Patricia Moran-Losada, Ting-Ting Lee, Jian Luo, Steven P Gygi, Jeffery W Kelly, Daniel Finley, Marius Wernig, Tony Wyss-Coray, Judith Frydman

{"title":"Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.","authors":"Ching-Chieh Chou, Ryan Vest, Miguel A Prado, Joshua Wilson-Grady, Joao A Paulo, Yohei Shibuya, Patricia Moran-Losada, Ting-Ting Lee, Jian Luo, Steven P Gygi, Jeffery W Kelly, Daniel Finley, Marius Wernig, Tony Wyss-Coray, Judith Frydman","doi":"10.1101/2023.03.27.534444","DOIUrl":"10.1101/2023.03.27.534444","url":null,"abstract":"Aging is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-Tau and Aβ, resembling those in AD patient and APP mouse brains. Quantitative tNeuron proteomics identify aging and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Supporting lysosomal deficits' centrality in AD, compounds ameliorating lysosomal function reduce Aβ deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of aging and AD.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Automatic multisensory integration follows subjective confidence rather than objective performance. 自动多感觉整合遵循主观信心而非客观表现。

bioRxiv : the preprint server for biology Pub Date : 2025-01-12 DOI: 10.1101/2023.06.07.544029

Yi Gao, Kai Xue, Brian Odegaard, Dobromir Rahnev

{"title":"Automatic multisensory integration follows subjective confidence rather than objective performance.","authors":"Yi Gao, Kai Xue, Brian Odegaard, Dobromir Rahnev","doi":"10.1101/2023.06.07.544029","DOIUrl":"10.1101/2023.06.07.544029","url":null,"abstract":"It is well known that sensory information from one modality can automatically affect judgments from a different sensory modality. However, it remains unclear what determines the strength of the influence of an irrelevant sensory cue from one modality on a perceptual judgment for a different modality. Here we test whether the strength of multisensory impact by an irrelevant sensory cue depends on participants' objective accuracy or subjective confidence for that cue. We created visual motion stimuli with low vs. high overall motion energy, where high-energy stimuli yielded higher confidence but lower accuracy in a visual-only task. We then tested the impact of the low- and high-energy visual stimuli on auditory motion perception. We found that the high-energy visual stimuli influenced the auditory motion judgments more strongly than the low-energy visual stimuli, consistent with their higher confidence but contrary to their lower accuracy. A computational model assuming common principles underlying confidence reports and multisensory integration captured these effects. Our findings show that automatic multisensory integration follows subjective confidence rather than objective performance and suggest the existence of common computations across vastly different stages of perceptual decision making.","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0