bioRxiv : the preprint server for biology最新文献

{"title":"Multiple Brain Activation Patterns for the Same Perceptual Decision-Making Task.","authors":"Johan Nakuci, Jiwon Yeon, Nadia Haddara, Ji-Hyun Kim, Sung-Phil Kim, Dobromir Rahnev","doi":"10.1101/2023.04.08.536107","DOIUrl":"10.1101/2023.04.08.536107","url":null,"abstract":"<p><p>Meaningful variation in internal states that impacts cognition and behavior remains challenging to discover and characterize. Here we leveraged trial-to-trial fluctuations in the brain-wide signal recorded using functional MRI to test if distinct sets of brain regions are activated on different trials when accomplishing the same task. Across three different perceptual decision-making experiments, we estimated the brain activations for each trial. We then clustered the trials based on their similarity using modularity-maximization, a data-driven classification method. In each experiment, we found multiple distinct but stable subtypes of trials, suggesting that the same task can be accomplished in the presence of widely varying brain activation patterns. Surprisingly, in all experiments, one of the subtypes exhibited strong activation in the default mode network, which is typically thought to decrease in activity during tasks that require externally focused attention. The remaining subtypes were characterized by activations in different task-positive areas. The default mode network subtype was characterized by behavioral signatures that were similar to the other subtypes exhibiting activation with task-positive regions. These findings demonstrate that the same perceptual decision-making task is accomplished through multiple brain activation patterns.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/65/nihpp-2023.04.08.536107v1.PMC10104176.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9351966","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}

{"title":"Single fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates.","authors":"Tingting Wu, Matthew R King, Yuanxin Qiu, Mina Farag, Rohit V Pappu, Matthew D Lew","doi":"10.1101/2023.01.26.525727","DOIUrl":"10.1101/2023.01.26.525727","url":null,"abstract":"<p><p>Biomolecular condensates are viscoelastic materials. Simulations predict that fluid-like condensations are defined by spatially inhomogeneous organization of the underlying molecules. Here, we test these predictions using single-fluorogen tracking and super-resolution imaging. Specifically, we leverage the localization and orientational preferences of freely diffusing fluorogens and the solvatochromic effect whereby specific fluorogens are turned on in response to condensate microenvironments. We deployed three different fluorogens to probe the microenvironments and molecular organization of different protein-based condensates. The spatiotemporal resolution and environmental sensitivity afforded by single-fluorogen imaging shows that the internal environments of condensates are more hydrophobic than coexisting dilute phases. Molecules within condensates are organized in a spatially inhomogeneous manner, and this gives rise to slow-moving nanoscale molecular clusters that coexist with fast-moving molecules. Fluorogens that localize preferentially to the interface help us map their distinct features. Our findings provide a structural and dynamical basis for the viscoelasticity of condensates.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668139","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}

{"title":"A gradual transition toward categorical representations along the visual hierarchy during working memory, but not perception.","authors":"Chaipat Chunharas, Michael J Wolff, Meike D Hettwer, Rosanne L Rademaker","doi":"10.1101/2023.05.18.541327","DOIUrl":"10.1101/2023.05.18.541327","url":null,"abstract":"<p><p>The ability to stably maintain visual information over brief delays is central to healthy cognitive functioning, as is the ability to differentiate such internal representations from external inputs. One possible way to achieve both is via multiple concurrent mnemonic representations along the visual hierarchy that differ systematically from the representations of perceptual inputs. To test this possibility, we examine orientation representations along the visual hierarchy during perception and working memory. Human participants directly viewed, or held in mind, oriented grating patterns, and the similarity between fMRI activation patterns for different orientations was calculated throughout retinotopic cortex. During direct viewing of grating stimuli, similarity was relatively evenly distributed amongst all orientations, while during working memory the similarity was higher around oblique orientations. We modeled these differences in representational geometry based on the known distribution of orientation information in the natural world: The \"veridical\" model uses an efficient coding framework to capture hypothesized representations during visual perception. The \"categorical\" model assumes that different \"psychological distances\" between orientations result in orientation categorization relative to cardinal axes. During direct perception, the veridical model explained the data well. During working memory, the categorical model gradually gained explanatory power over the veridical model for increasingly anterior retinotopic regions. Thus, directly viewed images are represented veridically, but once visual information is no longer tethered to the sensory world there is a gradual progression to more categorical mnemonic formats along the visual hierarchy.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667649","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}

{"title":"Bifurcation enhances temporal information encoding in the olfactory periphery.","authors":"Kiri Choi, Will Rosenbluth, Isabella R Graf, Nirag Kadakia, Thierry Emonet","doi":"10.1101/2024.05.27.596086","DOIUrl":"10.1101/2024.05.27.596086","url":null,"abstract":"<p><p>Living systems continually respond to signals from the surrounding environment. Survival requires that their responses adapt quickly and robustly to the changes in the environment. One particularly challenging example is olfactory navigation in turbulent plumes, where animals experience highly intermittent odor signals while odor concentration varies over many length- and timescales. Here, we show theoretically that Drosophila olfactory receptor neurons (ORNs) can exploit proximity to a bifurcation point of their firing dynamics to reliably extract information about the timing and intensity of fluctuations in the odor signal, which have been shown to be critical for odor-guided navigation. Close to the bifurcation, the system is intrinsically invariant to signal variance, and information about the timing, duration, and intensity of odor fluctuations is transferred efficiently. Importantly, we find that proximity to the bifurcation is maintained by mean adaptation alone and therefore does not require any additional feedback mechanism or fine-tuning. Using a biophysical model with calcium-based feedback, we demonstrate that this mechanism can explain the measured adaptation characteristics of Drosophila ORNs.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297432","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}

{"title":"Molecular logic for cellular specializations that initiate the auditory parallel processing pathways.","authors":"Junzhan Jing, Ming Hu, Tenzin Ngodup, Qianqian Ma, Shu-Ning Natalie Lau, Cecilia Ljungberg, Matthew J McGinley, Laurence O Trussell, Xiaolong Jiang","doi":"10.1101/2023.05.15.539065","DOIUrl":"10.1101/2023.05.15.539065","url":null,"abstract":"<p><p>The cochlear nuclear complex (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals, yet molecular logic governing cellular specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple new subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the remarkable cellular phenotypes in the CN. In particular, CN cell-type identity is encoded in a transcriptional architecture that orchestrates functionally congruent expression across a small set of gene families to customize projection patterns, input-output synaptic communication, and biophysical features required for encoding distinct aspects of acoustic signals. This high-resolution account of cellular heterogeneity from the molecular to the circuit level illustrates molecular logic for cellular specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/eb/nihpp-2023.05.15.539065v3.PMC10245571.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9691959","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}

{"title":"Basolateral amygdala oscillations enable fear learning in a biophysical model.","authors":"Anna Cattani, Don B Arnold, Michelle McCarthy, Nancy Kopell","doi":"10.1101/2023.04.28.538604","DOIUrl":"10.1101/2023.04.28.538604","url":null,"abstract":"<p><p>The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3-6 Hz), high theta (~6-12 Hz), and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it is not understood what role these rhythms play in supporting the plasticity. Here, we create a biophysically detailed model of the BLA circuit to show that several classes of interneurons (PV, SOM, and VIP) in the BLA can be critically involved in producing the rhythms; these rhythms promote the formation of a dedicated fear circuit shaped through spike-timing-dependent plasticity. Each class of interneurons is necessary for the plasticity. We find that the low theta rhythm is a biomarker of successful fear conditioning. The model makes use of interneurons commonly found in the cortex and, hence, may apply to a wide variety of associative learning situations.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/f2/nihpp-2023.04.28.538604v2.PMC10168360.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9992915","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}

{"title":"multimedia: Multimodal Mediation Analysis of Microbiome Data.","authors":"Hanying Jiang, Xinran Miao, Margaret W Thairu, Mara Beebe, Dan W Grupe, Richard J Davidson, Jo Handelsman, Kris Sankaran","doi":"10.1101/2024.03.27.587024","DOIUrl":"10.1101/2024.03.27.587024","url":null,"abstract":"<p><p>Mediation analysis has emerged as a versatile tool for answering mechanistic questions in microbiome research because it provides a statistical framework for attributing treatment effects to alternative causal pathways. Using a series of linked regressions, this analysis quantifies how complementary data relate to one another and respond to treatments. Despite these advances, existing software's rigid assumptions often result in users viewing mediation analysis as a black box. We designed the multimedia R package to make advanced mediation analysis techniques accessible, ensuring that statistical components are interpretable and adaptable. The package provides a uniform interface to direct and indirect effect estimation, synthetic null hypothesis testing, bootstrap confidence interval construction, and sensitivity analysis, enabling experimentation with various mediator and outcome models while maintaining a simple overall workflow. The software includes modules for regularized linear, compositional, random forest, hierarchical, and hurdle modeling, making it well-suited to microbiome data. We illustrate the package through two case studies. The first re-analyzes a study of the microbiome and metabolome of Inflammatory Bowel Disease patients, uncovering potential mechanistic interactions between the microbiome and disease-associated metabolites, not found in the original study. The second analyzes new data about the influence of mindfulness practice on the microbiome. The mediation analysis highlights shifts in taxa previously associated with depression that cannot be explained indirectly by diet or sleep behaviors alone. A gallery of examples and further documentation can be found at https://go.wisc.edu/830110.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10996591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869545","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}

{"title":"Characterization of the cellular components of mouse collecting lymphatic vessels reveals that lymphatic muscle cells are the innate pacemaker cells regulating lymphatic contractions.","authors":"S D Zawieja, G A Pea, S E Broyhill, A Patro, K H Bromert, C E Norton, H J Kim, S K Sivasankaran, M Li, J A Castorena-Gonzalez, B T Drumm, M J Davis","doi":"10.1101/2023.08.24.554619","DOIUrl":"10.1101/2023.08.24.554619","url":null,"abstract":"<p><p>Collecting lymphatic vessels (cLVs) exhibit spontaneous contractions with a pressure-dependent frequency, but the identity of the lymphatic pacemaker cell is still debated. By analogy to pacemakers in the GI and lower urinary tracts, proposed cLV pacemaker cells include interstitial cells of Cajal like cells (ICLC) or the lymphatic muscle (LMCs) cells themselves. Here we combined immunofluorescence and scRNAseq analyses with electrophysiological methods to examine the cellular constituents of the mouse cLV wall and assess whether any cell type exhibited morphological and functional processes characteristic of pacemaker cells: a continuous if not contiguous network integrated into the electrical syncytium; spontaneous Ca²⁺ transients; and depolarization-induced propagated contractions. We employed inducible Cre (iCre) mouse models routinely used to target these specific cell populations including: c-kitCreER ^<i>T2</i> to target ICLC; <i>PdgfrβCreER</i> ^<i>T2</i> to target pericyte-like cells; <i>PdgfrαCreER</i> ^<i>™</i> to target CD34⁺ adventitial cells and ICLC; and <i>Myh11CreER</i> ^<i>T2</i> to target LMCs directly. These specific inducible Cre lines were crossed to the fluorescent reporter ROSA26mT/mG, the genetically encoded Ca²⁺ sensor GCaMP6f, and the light-activated cation channel rhodopsin2 (ChR2). c-KitCreER ^<i>T2</i> labeled both a sparse population of LECs and round adventitial cells that responded to the mast cell activator compound 48-80. <i>PdgfrβCreER</i> ^<i>T2</i> drove recombination in both adventitial cells and LMCs, limiting its power to discriminate a pericyte-specific population. <i>PdgfrαCreER</i> ^<i>™</i> labeled a large population of interconnected, oak leaf-shaped cells primarily along the adventitial surface of the vessel. Of these cells, only LMCs consistently, but heterogeneously, displayed spontaneous Ca²⁺ events during the diastolic period of the contraction cycle, and whose frequency was modulated in a pressure-dependent manner. Optogenetic depolarization through the expression of ChR2 under control of <i>Myh11CreER</i> ^<i>T2</i> , but not <i>PdgfrαCreER</i> ^<i>™</i> or c-KitCreER ^<i>T2</i> , resulted in propagated contractions upon photo-stimulation. Membrane potential recordings in LMCs demonstrated that the rate of diastolic depolarization significantly correlated with contraction frequency. These findings support the conclusion that LMCs, or a subset of LMCs, are responsible for mouse cLV pacemaking.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178777","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}

{"title":"Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.","authors":"Kristina M Zvolanek, Jackson E Moore, Kelly Jarvis, Sarah J Moum, Molly G Bright","doi":"10.1101/2024.04.26.590312","DOIUrl":"10.1101/2024.04.26.590312","url":null,"abstract":"<p><p>Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n=12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923926","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}

{"title":"TIM-4 Identifies Effector B Cells Expressing a RORγt-Driven Proinflammatory Cytokine Module That Promotes Immune Responsiveness.","authors":"Qing Ding, Yufan Wu, Elena Torlai Triglia, Jennifer L Gommerman, Ayshwarya Subramanian, Vijay K Kuchroo, David M Rothstein","doi":"10.1101/2023.09.22.558524","DOIUrl":"10.1101/2023.09.22.558524","url":null,"abstract":"<p><p>B cells can express pro-inflammatory cytokines that promote a wide variety of immune responses. Here we show that B cells expressing the phosphatidylserine receptor TIM-4, preferentially express IL-17A, as well as IL-22, IL-6, IL-1β, and GM-CSF - a collection of cytokines reminiscent of pathogenic Th17 cells. Expression of this proinflammatory module requires IL-23R signaling and selective expression of RORγt and IL-17A by TIM-4⁺ B cells. TIM-4⁺ B cell-derived-IL-17A not only enhances the severity of experimental autoimmune encephalomyelitis (EAE) and promotes allograft rejection, but also acts in an autocrine manner to prevent their conversion into IL-10-expressing B cells with regulatory function. Thus, IL-17A acts as an inflammatory mediator and also enforces the proinflammatory activity of TIM-4⁺ B cells. Thus, TIM-4 serves as a broad marker for RORγt⁺ effector B cells (Beff) and allows further study of the signals regulating Beff differentiation and effector molecule expression.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/e7/nihpp-2023.09.22.558524v1.PMC10542535.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164499","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}