bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower-limb express visuomotor responses are spared in Parkinson’s Disease during step initiation from a stable position
Authors: Billen Lucas S. , Nonnekes Jorik , Corneil Brian D. , Weerdesteyn Vivian 
Published: November 2024

AbstractWhile motor impairments have been extensively studied in Parkinson’s Disease, rapid visuomotor transformations for flexible interaction with the environment have received surprisingly little attention. In recent years, such rapid visuomotor transformations have been studied in the form of express visuomotor responses (EVRs), which are goal-directed bursts of muscle activity that are thought to originate from superior colliculus, reaching the periphery via the tecto-reticulospinal pathway.Here, we examined EVRs in the lower limbs during goal-directed step initiation in 20 people with Parkison’s Disease (PwPD) and 20 age-matched healthy control participants (HC). As lower-limb EVRs in the young have been shown to interact with postural control - which is often affected in PwPD – we manipulated the postural demands by varying initial stance width and target location. In the low postural demand condition, EVRs were robustly present in both the PwPD (17/20) and HC (16/20) group. However, when postural demands were high, EVRs were largely absent in both groups and, instead, strong anticipatory postural adjustments (APAs) were required prior to foot off. EVR magnitudes were, on average, stronger in PwPD compared to HC, but they decreased with increasing disease severity, suggesting that the EVR network may become compromised or down-regulated in later stages of the disease. While APA magnitudes were smaller in PwPD compared to HC, subsequent stepping performance (step reaction time, duration, size, velocity) was remarkably similar between the two groups. We suggest that the EVR network may be upregulated in the early stages of Parkinson’s disease in order to compensate for some of the emerging motor deficits experienced in daily life.
Nonequilibrium brain dynamics elicited as the origin of perturbative complexity
Authors: Stikvoort Wiep , Pérez-Ordoyo Eider , Mindlin Iván , Escrichs Anira , Sitt Jacobo D. , Kringelbach Morten L. , Deco Gustavo , Perl Yonatan Sanz 
Published: November 2024

AbstractAssessing the level of consciousness someone is in, is not a trivial question and physicians have to rely on behavioural evaluations instead of quantifiable metrics. Many studies have empirically investigated measures related to the complexity elicited after the brain is stimulated to quantify and assess the level of consciousness across different states. Here we hypothesized that the level of non-equilibrium dynamics of the unperturbed brain already contains the information needed to know how the system will react to an external stimulus. We created personalized whole-brain models fitted to resting state fMRI data recorded in participants in different states of reduced consciousness (such as deep sleep and disorders of consciousness) to infer the effective connections underlying their brain dynamics. We then measured the out-of-equilibrium nature of the unperturbed brain by evaluating the level of asymmetry of the inferred connectivity, the time irreversibility in each model and compared this with the elicited complexity generated afterin silicoperturbations. Crucially, we found that states of reduced consciousness had a lower level of asymmetry in their effective connectivities compared to control subjects, as well as a lower level of irreversibility in their simulated dynamics, and a lower complexity. We demonstrated that the asymmetry in the underlying connections drives the nonequilibrium state of the system and in turn the differences in complexity as a response to the external stimuli.
Early changes in the properties of CA3 engram cells explored with a novel viral tool
Authors: Cupollilo Dario , Grosjean Noëlle , Marneffe Catherine , Viotti Julio , Reynaud Célia , Deforges Séverine , Carta Mario , Mulle Christophe 
Published: November 2024

ABSTRACTForming new memories after a one-time experience requires initial encoding then consolidation over time. During learning, multimodal information converges onto the hippocampus, activating sparse neuronal assemblies which are thought to form a memory representation through concerted activity and synaptic interconnectivity. In this work, we use a novel tool for fast-labeling of engram neurons (FLEN). FLEN is based on c-Fos activity-dependent transient expression of a destabilized fluorescent marker ZsGreen1 rapidly after one-trial learning. With FLEN, we explore the electrophysiological properties of c-Fos activated CA3 pyramidal neurons a few hours following one-trial learning of an episodic-like memory. In parallel, we employ the Robust Activity Marker (RAM) system, which provides activity-dependent labelling 24 hours following a novel experience. Comparing FLEN+ and RAM+ neurons allows to characterize how the properties of neuronal assemblies evolve during an initial phase of consolidation. Whereas no difference was observed in the excitability of FLEN+ vs. FLEN-neurons, RAM+ neurons were more excitable than RAM-neurons. This suggests that CA3 pyramidal neurons recruited in an engram progressively acquire increased excitability as compared to neurons which were not activated by the one-trial contextual memory task. In contrast, FLEN+ CA3 neurons show an increased number of excitatory inputs. Overall, with the FLEN strategy, we can show that both the intrinsic excitability and the synaptic properties of CA3 pyramidal neurons undergo progressive plastic changes over the first day following a one-trial memory task.
In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
Authors: Compans B. , Mastrolia V. , Lenherr C. , Burrone J. 
Published: November 2024

AbstractChemical synapses control their strength through the nanoscale clustering of postsynaptic receptors into sub-synaptic domains (SSDs). Despite their importance in synapse function, the properties and plasticity of these domains are not well understoodin vivo, particularly in inhibitory synapses. We used direct Stochastic Optical Resolution Microscopy (dSTORM) to show that Gephyrin, the main inhibitory receptor scaffold protein, is organised into SSDsin vivo, with distinct arrangements depending on their sub-cellular location and presynaptic partner. Furthermore, chronic chemogenetic increases in cortical activity caused a reduction in Gephyrin SSD volume specifically in axo-axonic, but not axo-dendritic, synapses. Functionally, this resulted in a weakening of axo-axonic contacts. We show that the nanoscale arrangement of synapses in the brain is plastic and used to fine-tune synaptic gainin vivo.
Holistic genetic barcoding reveals a lineage tree of tissue macrophage development
Authors: Frank Larissa , Postrach Daniel , Langhinrichs Maurice , Höfer Thomas , Rodewald Hans-Reimer 
Published: November 2024

AbstractTissue macrophages are crucial for organ development and homeostasis, yet the developmental routes leading to tissue macrophages remain controversial. By combining unbiasedPolyloxbarcoding with computational inference, we comprehensively mapped tissue macrophage ontogeny in mice from gastrulation to adult organs. Our data reveal a lineage tree of all tissue macrophages. This tree originates from a pan-hematopoietic progenitor at embryonic day (E)6.5 and branches, via oligolineage progenitors (E7.5-E9.5), into organ-specific macrophage lineages by E10.5. Barcode analysis in embryonic tissues and adult organ fragments suggests that local macrophage colonies, formed by organ-specific progenitors, persist into adulthood. Indeed, spatial fate mapping withPolytopebarcoding detects local Kupffer cell colonies of the size predicted by the lineage tree model. Our findings uncover the origin of tissue-resident macrophages from a lineage tree, and show how holistic barcoding can comprehensively map complex cellular lineage specification.One-Sentence SummaryHolistic, time- and space-resolved barcoding in the embryo reveals a unified lineage tree for all tissue macrophages, generating local macrophage colonies persisting in adult organs.
Increased fear generalization results in reduced generalization of extinction
Authors: Lopez-Moraga Alba , Gültekin Zeynep , Luyten Laura , Beckers Tom 
Published: November 2024

AbstractGeneralization of conditioned fear is adaptive for survival. However, overgeneralization of fear from threat cues to loosely similar yet safe stimuli is a hallmark of anxiety-related disorders. Such overgeneralization may moreover impact other fear learning processes. In particular, broad fear generalization might limit the effectiveness of extinction training, which may further maintain anxiety.Hypothesizing that increased generalization of conditioned fear might weaken the later generalization of fear extinction, we here compared rats conditioned with moderate-versus high-intensity foot shocks, the latter group expected to show stronger generalization of acquired fear than the former. Within each shock intensity group, we then conducted extinction training using the original conditioned stimulus (CS) for half of the animals and a generalization stimulus (GS) for the others. We found significantly less generalization of extinction to the CS if rats had initially been conditioned using the high-intensity foot shock than if they had been conditioned using the moderate-intensity foot shock, in line with our hypothesis.In conclusion, increased generalization of acquisition from a CS to a GS appears to go hand in hand with weaker generalization of extinction from that GS back to the CS. This may be important to consider in extinction-based exposure therapy because patients often present with broadly generalized fears, and exposure is usually not performed with the exact cues or situations for which fear was initially acquired.
Identification of clinical carbapenemases, 478 novel β-lactamases and putative seven new bacterial phyla from wastewater contaminated high arctic fjord sediments
Authors: Victor Manish P. , Øvreås Lise , Marathe Nachiket P. 
Published: November 2024

AbstractArctic microbiota is enigmatic and highly underexplored. With the aim of understanding the resistome and microbiota of high-Arctic fjord sediments and the effect of wastewater discharge on sediment microbiota, we analysed sediments using metagenomics. We show presence of 888 clinically relevant antibiotic resistance genes including genes coding resistance against last-resort antibiotics such as carbapenems, colistin, vancomycin, linezolid and tigecycline in sediment microbiota. Using computational models, 478 novel β-lactamases belonging to 217 novel β-lactamases families were revealed in sediment microbiota from Adventfjorden in Svalbard. We identified hosts for 69 novel gene families and showed that these genes are widespread in the Arctic environment. Further, in 644 metagenome-assembled genomes (MAGs) from sediment metagenomes >97% belong to novel taxa, representing seven putative novel phyla. These MAGs encoded important functions like nutrient cycling and methane metabolism etc. Our study demonstrated mixing of human associated bacteria and Arctic sediment microbiota. It provides the first comprehensive dataset of the distribution and diversity of novel microbes and β-lactamases in the high Arctic sediments.
Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies
Authors: Mahul-Mellier Anne-Laure , Altay Melek Firat , Maharjan Niran , Ait-Bouziad Nadine , Chiki Anass , Jagannath Somanath , Limorenko Galina , Novello Salvatore , Ricci Jonathan , Vingill Siv , Wade-Martins Richard , Holton Janice , Strand Catherine , Haikal Caroline , Li Jia-Yi , Hamelin Romain , Croisier Marie , Knott Graham , Mairet-Coello Georges , Weerens Laura , Michel Anne , Downey Patrick , Citron Martin , Lashuel Hilal A. 
Published: November 2024

AbstractAlpha-synuclein (aSyn) post-translational modifications (PTMs), particularly phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LBs), Lewy neurites, and other types of aSyn pathological aggregates in the brain of patients with Parkinson’s disease (PD) and other synucleinopathies. However, our knowledge about the precise role of PTMs in regulating the different stages of pathology formation, neurodegeneration, and aSyn pathology spreading remains incomplete. In this work, we applied a systematic approach to address this knowledge gap with an emphasis on mapping and elucidating the role of post-fibrillization C-terminal aSyn truncations in regulating the uptake, processing, seeding activity, and formation of LB-like inclusions and maturations in a well-established neuronal seeding model that recapitulates all the stages leading to LB formation and neurodegeneration. Our work shows that C-terminal cleavage of aSyn fibrils at multiple sites is a conserved process that occurs rapidly after and during the formation of intracellular LB-like aSyn inclusions in all neuronal seeding models. Interestingly, blocking the cleavage of internalized fibrils does not influence their seeding activity, whereas inhibiting the enzymes that regulate the cleavage of newly formed fibrils (e.g., calpains 1 and 2) significantly alters the formation of LB-like inclusions. We also show that C-terminal truncations, in combination with other PTMs, play a crucial role in regulating the interactome and remodeling of newly formed aSyn fibrils, including their shortening, lateral association, and packing during LB formation and maturation. Altogether, our results demonstrate that post-fibrillization C-terminal truncations have a differential role at different stages of aSyn aggregation and pathology formation. These insights, combined with the abundance of truncated aSyn species in LBs, have significant implications in understanding aSyn pathological diversity and developing therapeutic strategies targeting the C-terminus of aSyn or its proteolytic processing.
Embedded Extremum Seeking: A Bio-synthetic Optimiser
Authors: Smart Benjamin , Marucci Lucia , Renson Ludovic 
Published: November 2024

AbstractIn cybergentics, internal control uses synthetic genetic circuits to bypass the sensing and actuation limits of external control. Currently, embedded controllers are limited to basic controllers, like PID. Here, we introduce the Embedded Extremum Seeking Controller, the first example of a bio-synthetic optimiser. Extremum Seeking combines an integral and oscillator circuit to adjust system parameters and achieve a desired optimal steady state. This system uses an integral circuit and oscillator that already exist in synthetic biology. The Extremum Seeker is demonstratedin silicoon a Labour Division system, where the controller tunes a kinematic parameter, optimising the ratio of the culture subpopulations to maximise production. This controller paves the way for embedded controllers that precisely direct cellular behaviour without needing external actuation and sensing.
Gamma Synchrony Mediates Figure-Ground Perception
Authors: Karimian Maryam , Roberts Mark J. , De Weerd Peter , Senden Mario 
Published: November 2024

AbstractGamma synchrony is ubiquitous in visual cortex, but whether it contributes to perceptual grouping remains contentious based on observations that gamma frequency is not consistent across stimulus features and that gamma synchrony depends on distances between image elements. These stimulus dependencies have been argued to render synchrony among neural assemblies encoding components of the same object difficult. Alternatively, these dependencies may shape synchrony in meaningful ways. Using the theory of weakly coupled oscillators (TWCO), we demonstrate that stimulus dependence is crucial for gamma’s role in perception. Synchronization among coupled oscillators depends on frequency dissimilarity and coupling strength, which in early visual cortex relate to local feature dissimilarity and physical distance, respectively. We manipulated these factors in a texture segregation experiment wherein human observers identified the orientation of a figure defined by reduced contrast heterogeneity compared to the background. Human performance followed TWCO predictions both qualitatively and quantitatively, as formalized in a computational model. Moreover, we found that when enriched with a Hebbian learning rule, our model also predicted human learning effects. Increases in gamma synchrony due to perceptual learning predicted improvements in behavioral performance across sessions. This suggests that the stimulus-dependence of gamma synchrony is adaptable to the statistics of visual experiences, providing a viable neural grouping mechanism that can improve with visual experience. Together our results highlight the functional role of gamma synchrony in visual scene segmentation and provide a mechanistic explanation for its stimulus-dependent variability.
Kernel-based LFP estimation in detailed large-scale spiking network model of mouse visual cortex
Authors: Meneghetti Nicolò , Rimehaug Atle E. , Einevoll Gaute T. , Mazzoni Alberto , Ness Torbjørn V. 
Published: November 2024

SummarySimulations of large-scale neural activity are powerful tools for investigating neural networks. Calculating measurable brain signals like local field potentials (LFPs) bridges the gap between model predictions and experimental observations. However, accurately simulating LFPs from large-scale models has traditionally required highly detailed multicompartmental neuron models, posing significant computational challenges. Here, we demonstrate that a kernel-based method can efficiently and accurately estimate LFPs in a state-of-the-art multicompartmental model of the mouse primary visual cortex (V1). Beyond its computational efficiency, the kernel method aids analysis by disentangling contributions of individual neuronal populations to the LFP. Using this approach, we found that LFPs in the V1 model were dominated by external synaptic inputs, with local synaptic activity playing a minimal role. Our findings establish the kernel method as a powerful tool for LFP estimation in large-scale network models and for uncovering the synaptic mechanisms underlying brain signals.
An optical brain-machine interface reveals a causal role of posterior parietal cortex in goal-directed navigation
Authors: Sorrell Ethan , Wilson Daniel E. , Rule Michael E. , Yang Helen , Forni Fulvio , Harvey Christopher D. , O’Leary Timothy 
Published: November 2024

AbstractCortical circuits contain diverse sensory, motor, and cognitive signals, and form densely recurrent networks. This creates challenges for identifying causal relationships between neural populations and behavior. We developed a calcium imaging-based brain-machine interface (BMI) to study the role of posterior parietal cortex (PPC) in controlling navigation in virtual reality. By training a decoder to estimate navigational heading and velocity from PPC activity during virtual navigation, we discovered that mice could immediately navigate toward goal locations when control was switched to BMI. No learning or adaptation was observed during BMI, indicating that naturally occurring PPC activity patterns are sufficient to drive navigational trajectories in real time. During successful BMI trials, decoded trajectories decoupled from the mouse’s physical movements, suggesting that PPC activity relates to intended trajectories. Our work demonstrates a role for PPC in navigation and offers a BMI approach for investigating causal links between neural activity and behavior.
NaDyNet: A Toolbox for Dynamic Network Analysis of Naturalistic Stimuli
Authors: Yang Junjie , Hu Zhe , Li Junjing , Guo Xiaolin , Gao Xiaowei , Liu Jiaxuan , Wang Yaling , Qu Zhiheng , Li Wanchun , Li Zhongqi , Li Wanjing , Huang Yien , Chen Jiali , Wen Hao , Yuan Binke 
Published: November 2024

AbstractExperiments with naturalistic stimuli (e.g., listening to stories or watching movies) are emerging paradigms in brain function research. The content of naturalistic stimuli is rich and continuous. The fMRI signals of naturalistic stimuli are complex and include different components. A major challenge is isolate the stimuli-induced signals while simultaneously tracking the brain’s responses to these stimuli in real-time. To this end, we have developed a user-friendly graphical interface toolbox called NaDyNet (Naturalistic Dynamic Network Toolbox), which integrates existing dynamic brain network analysis methods and their enhanced versions. The main features of NaDyNet are: 1) extracting signals of interest from naturalistic fMRI signals; 2) incorporating six commonly used dynamic analysis methods and three static analysis methods; 3) enhanced versions of these dynamic methods by adopting inter-subject analysis to eliminate the effects of non-interest signals; 4) performing K-means clustering analysis to identify temporally reoccurring states along with their temporal and spatial attributes. We then introduced the rationale for incorporating inter-subject analysis to improve existing dynamic brain network analysis methods, and presented numerous examples. We also summarized research progress in comparing methodological efficacy, offered our recommendations for method selection in dynamic network analysis, and discussed the limitations of current approaches and directions for future research. We hope that this open source toolbox will promote the development of naturalistic neuroscience. The toolbox is available athttps://github.com/yuanbinke/Naturalistic-Dynamic-Network-Toolbox.
Acute restraint stress and pain modulation depend on the interaction between the periaqueductal gray and the lateral septum
Authors: Shah Devanshi Piyush , Chaudhury Yatika , Barik Arnab 
Published: November 2024

AbstractAcute restraint stress is known to cause analgesia in humans and laboratory animals, but the mechanisms are unknown. Recently, we have shown that a multi-nodal circuitry between the dorsal lateral septum (dLS)-lateral hypothalamic area (LHA)-rostral ventromedial medulla (RVM) plays an instructive role in restraint stress-induced analgesia. We found that the LS neurons are activated when mice struggle to escape the restraint, and we wondered about the origin of the escape signals. Hence, we performed retrograde viral labeling from the LS and found that the ventrolateral periaqueductal gray (vlPAG), a known anatomical substrate for escape behaviors, provides inputs to the LS. Through anatomical, behavioral, and in-vivo fiber photometry, we show that the PAG and LS neurons are synaptically connected; activation of either PAG or the post-synaptic LS neurons is sufficient to cause analgesia and sufficiently cause hyperalgesia. Moreover, we found that the LS neurons that receive inputs from PAG send axonal projections to the LHA. Together, we found that the vlPAG neurons encoding nociceptive and escape behaviors provide synaptic inputs to the dLS-LHA-RVM circuitry to mediate acute restraint stress-induced analgesia.Significance statementForced restraint causes stress, and this paradigm has been used in the laboratory to study the physiological effects of stress, including pain modulation. The dorsal lateral septum (LS) has been shown to mediate restraint-mediated stress and analgesia. It is unknown what signals encoded in the LS allow it to instruct stress and pain. A novel neural pathway between the periaqueductal gray (PAG) and LS is activated when mice try to escape the restraint. Repeated activity in the PAG-LS circuitry due to the inescapability of the restraint causes stress and analgesia