Spatiotemporal Activity Patterns Research Articles

Anti-Hebbian plasticity drives sequence learning in striatum

Spatio-temporal activity patterns have been observed in a variety of brain areas in spontaneous activity, prior to or during action, or in response to stimuli. Biological mechanisms endowing neurons with the ability to distinguish between different sequences remain largely unknown. Learning sequences of spikes raises multiple challenges, such as maintaining in memory spike history and discriminating partially overlapping sequences. Here, we show that anti-Hebbian spike-timing dependent plasticity (STDP), as observed at cortico-striatal synapses, can naturally lead to learning spike sequences. We design a spiking model of the striatal output neuron receiving spike patterns defined as sequential input from a fixed set of cortical neurons. We use a simple synaptic plasticity rule that combines anti-Hebbian STDP and non-associative potentiation for a subset of the presented patterns called rewarded patterns. We study the ability of striatal output neurons to discriminate rewarded from non-rewarded patterns by firing only after the presentation of a rewarded pattern. In particular, we show that two biological properties of striatal networks, spiking latency and collateral inhibition, contribute to an increase in accuracy, by allowing a better discrimination of partially overlapping sequences. These results suggest that anti-Hebbian STDP may serve as a biological substrate for learning sequences of spikes.

Spatiotemporal organization of prefrontal norepinephrine influences neuronal activity.

Norepinephrine (NE), a neuromodulator released by locus coeruleus (LC) neurons throughout cortex, influences arousal and learning through extra-synaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the prefrontal cortex (PFC) affect neuronal firing, we employed in vivo two-photon imaging of layer 2/3 of PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. In this proof of principle study, we found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to create a heterogeneous NE field. Utilizing generalized linear models, we demonstrated that cellular Ca2+ fluctuations are influenced by both the local and global NE field. However, during periods of local/global NE field decoupling, the local field drives cell firing dynamics rather than the global field. These findings underscore the significance of localized, phasic NE fluctuations for structuring cell firing, which may provide local neuromodulatory control of cortical activity.Significance Statement NE is a neuromodulator which plays a critical role in learning and arousal, but understanding its spatial scale has been limited by technical barriers. Here, we utilized two-photon imaging of GPCR-based sensors, light sheet imaging, and computational modeling to gain insight into the fine scale organization of NE in PFC. We found that NE can influence neuronal activity at a local scale within cortex, which has not been shown before, and we developed new computational approaches to analyzing two-photon imaging of GPCR based fluorescent sensors. This insight will facilitate improved understanding of NE's role in motivated behaviors, as well as new approaches for understanding local neurotransmitter function.

Migraine aura discrimination using machine learning: an fMRI study during ictal and interictal periods.

Functional magnetic resonance imaging (fMRI) studies on migraine with aura are challenging due to the rarity of patients with triggered cases. This study optimized methodologies to explore differences in ictal and interictal spatiotemporal activation patterns based on visual stimuli using fMRI in two patients with unique aura triggers. Both patients underwent separate fMRI sessions during the ictal and interictal periods. The Gaussian Process Classifier (GPC) was used to differentiate these periods by employing a machine learning temporal embedding approach and spatiotemporal activation patterns based on visual stimuli. When restricted to visual and occipital regions, GPC had an improved performance, with accuracy rates for patients A and B of roughly 86-90% and 77-81%, respectively (p < 0.01). The algorithm effectively differentiated visual stimulation and rest periods and identified times when aura symptoms manifested, as evident from the varying predicted probabilities in the GPC models. These findings contribute to our understanding of the role of visual processing and brain activity patterns in migraine with aura and the significance of temporal embedding techniques in examining aura phenomena. This finding has implications for diagnostic tools and therapeutic techniques, especially for patients suffering from aura symptoms.

Flying by the river side: Survey of bat distributions and environmental contexts along a 1000‐mile river corridor, Green and Colorado Rivers, USA

AbstractAimEmerging research shows how bioindicators, specifically bats, can serve as a means for monitoring conservation and management of riparian corridors for multiple taxonomic groups. To track changes in the composition or abundance of bioindicator species, researchers must attain a baseline in species presence and relative activity. We examined the spatial and temporal patterns of bat community composition and activity along a 1000‐mile river corridor to determine species diversity trends by latitude and habitat.LocationColorado River Basin.MethodsHere we describe the results from an acoustic bat survey conducted opportunistically on the 2019 Sesquicentennial Colorado River Exploring Expedition. This broad, 1000‐mile survey provides a baseline for species distributions over a large geographic range.ResultsIn total, we collected 63 nights of acoustic data over 70 days and recorded over 59,000 files equating to 45,363 caLL files (≥2 pulses). 18,490 (41% of caLL files) were identified as species (n = 19 bat species). We applied non‐metric multidimensional scaling to characterize spatiotemporal patterns of activity between species, as well as compared bat activity among river features and local environmental conditions (i.e., temperature and time since sunset) using an information theoretic approach.ConclusionSpecies composition varied by physiographic region and adjacent river habitat, thus providing a quantifiable measure of determining habitat quality along this major river system and providing baseline information for using bats as bioindicators of habitat quality.

Human mobility reshaped? Deciphering the impacts of the Covid-19 pandemic on activity patterns, spatial habits, and schedule habits

Despite the historically documented regularity in human mobility patterns, the relaxation of spatial and temporal constraints, brought by the widespread adoption of telecommuting and e-commerce during the COVID-19 pandemic, as well as a growing desire for flexible work arrangements in a post-pandemic work, indicates a potential reshaping of these patterns. In this paper, we investigate the multifaceted impacts of relaxed spatio-temporal constraints on human mobility, using well-established metrics from the travel behavior literature. Further, we introduce a novel metric for schedule regularity, accounting for specific day-of-week characteristics that previous approaches overlooked. Building on the large body of literature on the impacts of COVID-19 on human mobility, we make use of passively tracked Point of Interest (POI) data for approximately 21,700 smartphone users in the US, and analyze data between January 2020 and September 2022 to answer two key questions: (1) has the COVID-19 pandemic and its associated relaxation of spatio-temporal activity patterns reshaped the different aspects of human mobility, and (2) have we achieved a state of stable post-pandemic “new normal”? We hypothesize that the relaxation of the spatiotemporal constraints around key activities will result in people exhibiting less regular schedules. Findings reveal a complex landscape: while some mobility indicators have reverted to pre-pandemic norms, such as trip frequency and travel distance, others, notably at-home dwell-time, persist at altered levels, suggesting a recalibration rather than a return to past behaviors. Most notably, our analysis reveals a paradox: despite the documented large-scale shift towards flexible work arrangements, schedule habits have strengthened rather than relaxed, defying our initial hypotheses and highlighting a desire for regularity. The study’s results contribute to a deeper understanding of the post-pandemic “new normal”, offering key insights on how multiple facets of travel behavior were reshaped, if at all, by the COVID-19 pandemic, and will help inform transportation planning in a post-pandemic world.

A Systematic Review of the Potential Influence of Urbanization on the Regional Thunderstorm Process and Lightning Activity

In the context of global climate change, lightning disasters have emerged as a serious environmental factor that restricts the sustainable development of megacities. This paper provides a review of the research on the impact of urbanization on thunderstorm processes and lightning activity, exploring various aspects, such as aerosols, urban thermal effects, urban dynamic effects, and building morphology. Despite numerous significant achievements in the study of the impact of air pollutants on lightning activity, there is no consensus on whether aerosols serve to enhance or inhibit lightning activity. The temperature difference between the urban underlying surface and the natural underlying surface could sustain and promote the occurrence and development of convective systems, thus enhancing lightning activity. In terms of urban dynamics, the barrier effect has led to the maximum center of lightning appearing at the edge of a built-up area, which might be associated with factors, such as urban heat island (UHI) intensity, wind speed, synoptic background, and city size. Additionally, the size of a city and the height of the buildings was also an influencing factor on lightning activity. In summary, scholars have made progress in understanding the characteristics and drivers of urban lightning activity in recent years, but there are still some urgent problems that need to be solved: (1) How to analyze, comprehensively, the spatiotemporal patterns of urban lightning activity under different thunderstorm intensity backgrounds? (2) How to conduct analysis to investigate the influence of alterations in the boundary layer structure, water–heat energy balance, and water vapor circulation processes on urban lightning activity in the context of urbanization? (3) How to couple numerical models of different scales to enhance the understanding of the impact of complex underlying surfaces on urban lightning activity? Future studies could investigate the relationship between urbanization and thunderstorm/lightning activity using a combination of observational data, numerical modeling, and laboratory experiments, which holds promise for providing valuable theoretical insights and technical support to enhance the prediction, nowcasting, early warning, and risk assessment of thunderstorms and lightning in urban areas.

Alpha and Beta Oscillations Differentially Support Word Production in a Rule-Switching Task.

Research into the role of brain oscillations in basic perceptual and cognitive functions has suggested that the alpha rhythm reflects functional inhibition while the beta rhythm reflects neural ensemble (re)activation. However, little is known regarding the generalization of these proposed fundamental operations to linguistic processes, such as speech comprehension and production. Here, we recorded magnetoencephalography in participants performing a novel rule-switching paradigm. Specifically, Dutch native speakers had to produce an alternative exemplar from the same category or a feature of a given target word embedded in spoken sentences (e.g., for the word "tuna", an exemplar from the same category-"seafood"-would be "shrimp", and a feature would be "pink"). A cue indicated the task rule-exemplar or feature-either before (pre-cue) or after (retro-cue) listening to the sentence. Alpha power during the working memory delay was lower for retro-cue compared with that for pre-cue in the left hemispheric language-related regions. Critically, alpha power negatively correlated with reaction times, suggestive of alpha facilitating task performance by regulating inhibition in regions linked to lexical retrieval. Furthermore, we observed a different spatiotemporal pattern of beta activity for exemplars versus features in the right temporoparietal regions, in line with the proposed role of beta in recruiting neural networks for the encoding of distinct categories. Overall, our study provides evidence for the generalizability of the role of alpha and beta oscillations from perceptual to more "complex, linguistic processes" and offers a novel task to investigate links between rule-switching, working memory, and word production.

Putative Spatiotemporal Changes in Inhibitor Activity during Cold Stratification of Sapium sebiferum Seeds

Putative Spatiotemporal Changes in Inhibitor Activity during Cold Stratification of Sapium sebiferum Seeds

A review of bovine tuberculosis transmission risk in European wildlife communities

Abstract Understanding how disease moves through wildlife communities is essential to managing outbreaks of zoonotic diseases across the globe. Bovine tuberculosis is a disease caused by the bacterium Mycobacterium bovis that can threaten domestic and wildlife species. The mechanism by which Mycobacterium bovis is spread between species is still poorly understood. Previous reviews are limited in the breadth of species considered and are primarily concerned with transmission from wildlife to domestic species. We conducted a review and analysis of Mycobacterium bovis prevalence rates in European wildlife species to identify species of concern for the transmission of bovine tuberculosis in a wildlife community. We subsequently conducted a narrative review of these species assessing the risk of Mycobacterium bovis transmission in a wildlife community based on available literature. We calculated weighted mean disease prevalence rates to be highest in fallow deer (Dama dama, 20%), Eurasian badgers (Meles meles, 11%), wild boar (Sus scrofa, 9%) and red foxes (Vulpes vulpes, 4%). We considered these species to be of particular concern for the transmission of Mycobacterium bovis and selected them as the focus of our narrative review and risk assessment. Our risk assessment considered disease pathology, spatiotemporal activity patterns and animal behaviour as factors affecting the likelihood of Mycobacterium bovis transmission between wildlife species. We found that prior research has principally focused on a few individual species, but that Mycobacterium bovis transmission through a wildlife community is likely more complex. We determined that disease transmission between multiple species may compound the severity of an outbreak of bovine tuberculosis. Broad, multi‐species sampling campaigns and standardised Mycobacterium bovis testing protocols should be implemented in future studies. We also determined that an in‐depth analysis of spatiotemporal overlap between species was needed to better assess the risk of transmission between wildlife species.

Neural signatures of shared subjective affective engagement and disengagement during movie viewing.

When watching a negative emotional movie, we differ from person to person in the ease with which we engage and the difficulty with which we disengage throughout a temporally evolving narrative. We investigated neural responses of emotional processing, by considering inter-individual synchronization in subjective emotional engagement and disengagement. The neural underpinnings of these shared responses are ideally studied in naturalistic scenarios like movie viewing, wherein individuals emotionally engage and disengage at their own time and pace throughout the course of a narrative. Despite the rich data that naturalistic designs can bring to the study, there is a challenge in determining time-resolved behavioral markers of subjective engagement and disengagement and their underlying neural responses. We used a within-subject cross-over design instructing 22 subjects to watch clips of either neutral or sad content while undergoing functional magnetic resonance imaging (fMRI). Participants watched the same movies a second time while continuously annotating the perceived emotional intensity, thus enabling the mapping of brain activity and emotional experience. Our analyses revealed that between-participant similarity in waxing (engagement) and waning (disengagement) of emotional intensity was directly related to the between-participant similarity in spatiotemporal patterns of brain activation during the movie(s). Similar patterns of engagement reflected common activation in the bilateral ventromedial prefrontal cortex, regions often involved in self-referenced evaluation and generation of negative emotions. Similar patterns of disengagement reflected common activation in central executive and default mode network regions often involved in top-down emotion regulation. Together this work helps to better understand cognitive and neural mechanisms underpinning engagement and disengagement from emotionally evocative narratives.

LUR modeling of long-term average hourly concentrations of NO2 using hyperlocal mobile monitoring data

Mobile monitoring campaigns have effectively captured spatial hyperlocal variations in long-term average concentrations of regulated and unregulated air pollutants. However, their application in estimating spatiotemporally varying maps has rarely been investigated. Tackling this gap, we investigated whether mobile measurements can assess long-term average nitrogen dioxide (NO2) concentrations for each hour of the day. Using mobile NO2 data monitored for 10 months in Amsterdam, we examined the performance of two spatiotemporal land use regression (LUR) methods, Spatiotemporal-Kriging and GTWR (Geographical and Temporal Weighted Regression), alongside two classical spatial LUR models developed separately for each hour. We found that mobile measurements follow the general pattern of fixed-site measurements, but with considerable deviations (indicating collection uncertainty). Leveraging heterogeneous spatiotemporal autocorrelations, GTWR smoothed these deviations and achieved an overall performance of an R2 of 0.49 and a Mean Absolute Error of 6.33 μg/m3, validated by long-term fixed-site measurements (out-of-sample). The other models tested were more affected by the collection uncertainty. We highlighted that the spatiotemporal variations captured in mobile measurements can be used to reconstruct long-term average hourly air pollution maps. These maps facilitate dynamic exposure assessments considering spatiotemporal human activity patterns.

A method for detecting spatiotemporal patterns of cancer biomarkers-evoked activity using radial basis function network extracted time-domain features from calcium imaging data

BackgroundTwo-photon calcium imaging is widely used to study the odor-evoked glomerular activity in the dorsal olfactory bulb of macrosmatic animals. The nonstationary character of activated patterns sets a limit on the use of a traditional image processing approaches. New methodThe developed method makes it possible to automatically map cancer biomarkers-activated glomeruli in the rat dorsal olfactory bulb. We interpolated fluorescence intensity of calcium dynamics based on the Gaussian RBF network and synthesized the physiological fluorescence model of the receptive glomerular field. ResultsThe experiments on 5 rats confirmed the correctness of the developed approach. Patterns evoked by the 6-methyl-5-hepten-2-one (stomach cancer biomarker) and benzene (lung cancer biomarker) were correctly identified. Comparison with existing methodsThe proposed method was compared with the nonnegative matrix factorization method and with the method based on computer vision algorithms. The developed approach showed better accuracy in experiments and provided the mathematical models of the odor-evoked patterns synthesis. These models can be used to generate synthetic images of odor-evoked glomerular activity and thus to overcome the problem of small experimental data collected in calcium imaging. ConclusionsThe proposed method should be considered part of the toolkit for fully automatic analysis of calcium imaging-based studies. Currently available methodology is not able to use breath biomarkers to reliably discriminate between cancer patients and healthy controls. Nevertheless, the effective identification of the spatial patterns of cancer biomarkers-evoked glomerular activity can serve as the foundation for highly sensitive biohybrid systems for cancer screening.

Spike sorting in the presence of stimulation artifacts: a dynamical control systems approach

Objective. Bi-directional electronic neural interfaces, capable of both electrical recording and stimulation, communicate with the nervous system to permit precise calibration of electrical inputs by capturing the evoked neural responses. However, one significant challenge is that stimulation artifacts often mask the actual neural signals. To address this issue, we introduce a novel approach that employs dynamical control systems to detect and decipher electrically evoked neural activity despite the presence of electrical artifacts. Approach. Our proposed method leverages the unique spatiotemporal patterns of neural activity and electrical artifacts to distinguish and identify individual neural spikes. We designed distinctive dynamical models for both the stimulation artifact and each neuron observed during spontaneous neural activity. We can estimate which neurons were active by analyzing the recorded voltage responses across multiple electrodes post-stimulation. This technique also allows us to exclude signals from electrodes heavily affected by stimulation artifacts, such as the stimulating electrode itself, yet still accurately differentiate between evoked spikes and electrical artifacts. Main results. We applied our method to high-density multi-electrode recordings from the primate retina in an ex vivo setup, using a grid of 512 electrodes. Through repeated electrical stimulations at varying amplitudes, we were able to construct activation curves for each neuron. The curves obtained with our method closely resembled those derived from manual spike sorting. Additionally, the stimulation thresholds we estimated strongly agreed with those determined through manual analysis, demonstrating high reliability ( R2=0.951 for human 1 and R2=0.944 for human 2). Significance. Our method can effectively separate evoked neural spikes from stimulation artifacts by exploiting the distinct spatiotemporal propagation patterns captured by a dense, large-scale multi-electrode array. This technique holds promise for future applications in real-time closed-loop stimulation systems and for managing multi-channel stimulation strategies.

Resource-Efficient Neural Network Architectures for Classifying Nerve Cuff Recordings on Implantable Devices.

Closed-loop functional electrical stimulation can use recorded nerve signals to create implantable systems that make decisions regarding nerve stimulation in real-time. Previous work demonstrated convolutional neural network (CNN) discrimination of activity from different neural pathways recorded by a high-density multi-contact nerve cuff electrode, achieving state-of-the-art performance but requiring too much data storage and power for a practical implementation on surgically implanted hardware. To reduce resource utilization for an implantable implementation, with minimal performance loss for CNNs that can discriminate between neural pathways in multi-contact cuff electrode recordings. Neural networks (NNs) were evaluated using rat sciatic nerve recordings previously collected using 56-channel cuff electrodes to capture spatiotemporal neural activity patterns. NNs were trained to classify individual, natural compound action potentials (nCAPs) elicited by sensory stimuli. Three architectures were explored: the previously reported ESCAPE-NET, a fully convolutional network, and a recurrent neural network. Variations of each architecture were evaluated based on F1-score, number of weights, and floating-point operations (FLOPs). NNs were identified that, when compared to ESCAPE-NET, require 1,132-1,787x fewer weights, 389-995x less memory, and 6-11,073x fewer FLOPs, while maintaining macro F1-scores of 0.70-0.71 compared to a baseline of 0.75. Memory requirements range from 22.69 KB to 58.11 KB, falling within on-chip memory sizes from published deep learning accelerators fabricated in ASIC technology. Reduced versions of ESCAPE-NET require significantly fewer resources without significant accuracy loss, thus can be more easily incorporated into a surgically implantable device that performs closed-loop responsive neural stimulation.

ST-SCGNN: A Spatio-Temporal Self-Constructing Graph Neural Network for Cross-Subject EEG-Based Emotion Recognition and Consciousness Detection.

In this paper, a novel spatio-temporal self-constructing graph neural network (ST-SCGNN) is proposed for cross-subject emotion recognition and consciousness detection. For spatio-temporal feature generation, activation and connection pattern features are first extracted and then combined to leverage their complementary emotion-related information. Next, a self-constructing graph neural network with a spatio-temporal model is presented. Specifically, the graph structure of the neural network is dynamically updated by the self-constructing module of the input signal. Experiments based on the SEED and SEED-IV datasets showed that the model achieved average accuracies of 85.90% and 76.37%, respectively. Both values exceed the state-of-the-art metrics with the same protocol. In clinical besides, patients with disorders of consciousness (DOC) suffer severe brain injuries, and sufficient training data for EEG-based emotion recognition cannot be collected. Our proposed ST-SCGNN method for cross-subject emotion recognition was first attempted in training in ten healthy subjects and testing in eight patients with DOC. We found that two patients obtained accuracies significantly higher than chance level and showed similar neural patterns with healthy subjects. Covert consciousness and emotion-related abilities were thus demonstrated in these two patients. Our proposed ST-SCGNN for cross-subject emotion recognition could be a promising tool for consciousness detection in DOC patients.

Downstream network transformations dissociate neural activity from causal functional contributions

Neuroscientists rely on distributed spatio-temporal patterns of neural activity to understand how neural units contribute to cognitive functions and behavior. However, the extent to which neural activity reliably indicates a unit's causal contribution to the behavior is not well understood. To address this issue, we provide a systematic multi-site perturbation framework that captures time-varying causal contributions of elements to a collectively produced outcome. Applying our framework to intuitive toy examples and artificial neural networks revealed that recorded activity patterns of neural elements may not be generally informative of their causal contribution due to activity transformations within a network. Overall, our findings emphasize the limitations of inferring causal mechanisms from neural activities and offer a rigorous lesioning framework for elucidating causal neural contributions.

Understanding the effect of white matter delays on large scale brain synchrony

The presence of myelin is a powerful structural factor that controls the conduction speed of mammalian axons. It is the combination of local synaptic activity and non-local delayed axonal interactions within the cortex that is believed to be the major source of large-scale brain signals that can be readily observed with modern neuroimaging modalities. Here, we present perspectives from neural mass and network modelling and develop a new set of mathematical tools able to unravel the contributions of space-dependent axonal delays to large-scale spatiotemporal patterning of brain activity. We first analyse a single neuronal population Wilson–Cowan neural mass model with self-feedback and a single delay and show how to construct periodic orbits for a Heaviside firing rate. For this nonsmooth model we perform linear stability analysis by augmenting Floquet theory with saltation operations. Building on this example, we then show how to treat the synchronous oscillatory state in networks of nonsmooth neural masses with multiple and heterogeneous delays. Theoretical predictions for the parameter variations that lead to instabilities of the synchronous network state and the excitation of structured spatio-temporal activity patterns are confirmed with direct numerical simulations.

A hybrid spatiotemporal deep belief network and sparse representation-based framework reveals multilevel core functional components in decoding multitask fMRI signals.

Decoding human brain activity on various task-based functional brain imaging data is of great significance for uncovering the functioning mechanism of the human mind. Currently, most feature extraction model-based methods for brain state decoding are shallow machine learning models, which may struggle to capture complex and precise spatiotemporal patterns of brain activity from the highly noisy fMRI raw data. Moreover, although decoding models based on deep learning methods benefit from their multilayer structure that could extract spatiotemporal features at multiscale, the relatively large populations of fMRI datasets are indispensable, and the explainability of their results is elusive. To address the above problems, we proposed a computational framework based on hybrid spatiotemporal deep belief network and sparse representations to differentiate multitask fMRI (tfMRI) signals. Using a relatively small cohort of tfMRI data as a test bed, our framework can achieve an average classification accuracy of 97.86% and define the multilevel temporal and spatial patterns of multiple cognitive tasks. Intriguingly, our model can characterize the key components for differentiating the multitask fMRI signals. Overall, the proposed framework can identify the interpretable and discriminative fMRI composition patterns at multiple scales, offering an effective methodology for basic neuroscience and clinical research with relatively small cohorts.

Spatiotemporal-social association predicts immunological similarity in rewilded mice.

Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual's interaction with its environment. We therefore tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including associations measured from spatiotemporal co-occurrences, to immune phenotypes. We found extensive variation in individual and social behavior among and within mouse strains upon rewilding. In addition, we found that the more associated two individuals were, the more similar their immune phenotypes were. Spatiotemporal association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or shared infection status. These results highlight the importance of shared spatiotemporal activity patterns and/or social networks for immune phenotype and suggest potential immunological correlates of social life.

Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles

Rho GTPases play a key role in the spatio-temporal coordination of cytoskeletal dynamics during cell migration. Here, we directly investigate crosstalk between the major Rho GTPases Rho, Rac and Cdc42 by combining rapid activity perturbation with activity measurements in mammalian cells. These studies reveal that Rac stimulates Rho activity. Direct measurement of spatio-temporal activity patterns show that Rac activity is tightly and precisely coupled to local cell protrusions, followed by Rho activation during retraction. Furthermore, we find that the Rho-activating Lbc-type GEFs Arhgef11 and Arhgef12 are enriched at transient cell protrusions and retractions and recruited to the plasma membrane by active Rac. In addition, their depletion reduces activity crosstalk, cell protrusion-retraction dynamics and migration distance and increases migration directionality. Thus, our study shows that Arhgef11 and Arhgef12 facilitate exploratory cell migration by coordinating cell protrusion and retraction by coupling the activity of the associated regulators Rac and Rho.