Voltage mapping in subcellular nanodomains using electro-diffusion modeling.

Voltage distribution in sub-cellular micro-domains such as neuronal synapses, small protrusions, or dendritic spines regulates the opening and closing of ionic channels, energy production, and thus, cellular homeostasis and excitability. Yet how voltage changes at such a small scale in vivo remains challenging due to the experimental diffraction limit, large signal fluctuations, and the still limited resolution of fast voltage indicators. Here, we study the voltage distribution in nano-compartments using a computational approach based on the Poisson-Nernst-Planck equations for the electro-diffusion motion of ions, where inward and outward fluxes are generated between channels.

Astroglial gap junctions strengthen hippocampal network activity by sustaining afterhyperpolarization via KCNQ channels.

Throughout the brain, astrocytes form networks mediated by gap junction channels that promote the activity of neuronal ensembles. Although their inputs on neuronal information processing are well established, how molecular gap junction channels shape neuronal network patterns remains unclear. Here, using astroglial connexin-deficient mice, in which astrocytes are disconnected and neuronal bursting patterns are abnormal, we show that astrocyte networks strengthen bursting activity via dynamic regulation of extracellular potassium levels, independently of glutamate homeostasis or metabolic support.

Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles.

Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism.

Analyzing Photoactivation with Diffusion Models to Study Transport in the Endoplasmic Reticulum Network.

Photoactivation is a paradigm consisting in local molecular fluorescent activation by laser illumination in a chosen region (source) while measuring the concentration at a target region. Data-driven modeling is concerned with the following questions: how from the measurement in these two regions is it possible to infer the properties of molecular propagation? How is it possible to use such responses to infer motions occurring in networks such as the endoplasmic reticulum? In this book chapter, we shall review the data-driven analysis based on diffusion-transport models and numerical simulations to interpret the photoactivation dynamics and extract biophysical parameters. We will discuss modeling approaches to reconstruct local network properties from photoactivation transients.

Chromatin phase separated nanoregions explored by polymer cross-linker models and reconstructed from single particle trajectories.

Phase separated domains (PSDs) are ubiquitous in cell biology, representing nanoregions of high molecular concentration. PSDs appear at diverse cellular domains, such as neuronal synapses but also in eukaryotic cell nucleus, limiting the access of transcription factors and thus preventing gene expression. We develop a generalized cross-linker polymer model, to study PSDs: we show that increasing the number of cross-linkers induces a polymer condensation, preventing access of diffusing molecules.

Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries.

Topologically Associating Domains (TADs) separate vertebrate genomes into insulated regulatory neighborhoods that focus genome-associated processes. TADs are formed by Cohesin-mediated loop extrusion, with many TAD boundaries consisting of clustered binding sites of the CTCF insulator protein. Here we determine how this clustering of CTCF binding contributes to the blocking of loop extrusion and the insulation between TADs.

Diversity of dynamic voltage patterns in neuronal dendrites revealed by nanopipette electrophysiology.

Dendrites and dendritic spines are the essential cellular compartments in neuronal communication, conveying information through transient voltage signals. Our understanding of these compartmentalized voltage dynamics in fine, distal neuronal dendrites remains poor due to the difficulties inherent to accessing and stably recording from such small, nanoscale cellular compartments for a sustained time. To overcome these challenges, we use nanopipettes that permit long and stable recordings directly from fine neuronal dendrites.

Spectral EEG correlations from the different phases of general anesthesia.

Introduction: Electroencephalography (EEG) signals contain transient oscillation patterns commonly used to classify brain states in responses to action, sleep, coma or anesthesia.

Methods: Using a time-frequency analysis of the EEG, we search for possible causal correlations between the successive phases of general anesthesia. We hypothesize that it could be possible to anticipate recovery patterns from the induction or maintenance phases.

Predicting neurological outcome after cardiac arrest by combining computational parameters extracted from standard and deviant responses from auditory evoked potentials.

Background: Despite multimodal assessment (clinical examination, biology, brain MRI, electroencephalography, somatosensory evoked potentials, mismatch negativity at auditory evoked potentials), coma prognostic evaluation remains challenging.

Methods: We present here a method to predict the return to consciousness and good neurological outcome based on classification of auditory evoked potentials obtained during an oddball paradigm. Data from event-related potentials (ERPs) were recorded noninvasively using four surface electroencephalography (EEG) electrodes in a cohort of 29 post-cardiac arrest comatose patients (between day 3 and day 6 following admission).

Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca channels drives sustained active zone potentiation.

At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at AZs undergoing presynaptic homeostatic potentiation.

Data-driven multiscale dynamical framework to control a pandemic evolution with non-pharmaceutical interventions.

Before the availability of vaccines, many countries have resorted multiple times to drastic social restrictions to prevent saturation of their health care system, and to regain control over an otherwise exponentially increasing COVID-19 pandemic. With the advent of data-sharing, computational approaches are key to efficiently control a pandemic with non-pharmaceutical interventions (NPIs). Here we develop a data-driven computational framework based on a time discrete and age-stratified compartmental model to control a pandemic evolution inside and outside hospitals in a constantly changing environment with NPIs.

Dynamic Regulation of Mitochondrial [Ca] in Hippocampal Neurons.

While neuronal mitochondria have been studied extensively in their role in health and disease, the rules that govern calcium regulation in mitochondria remain somewhat vague. In the present study using cultured rat hippocampal neurons transfected with the mtRCaMP mitochondrial calcium sensor, we investigated the effects of cytosolic calcium surges on the dynamics of mitochondrial calcium ([Ca]m). Cytosolic calcium ([Ca]c) was measured using the high affinity sensor Fluo-2.

Computational methods and diffusion theory in triangulation sensing to model neuronal navigation.

Computational methods are now recognized as powerful and complementary approaches in various applied sciences such as biology. These computing methods are used to explore the gap between scales such as the one between molecular and cellular. Here we present recent progress in the development of computational approaches involving diffusion modeling, asymptotic analysis of the model partial differential equations, hybrid methods and simulations in the generic context of cell sensing and guidance via external gradients.

High-throughput super-resolution single-particle trajectory analysis reconstructs organelle dynamics and membrane reorganization.

Super-resolution imaging can generate thousands of single-particle trajectories. These data can potentially reconstruct subcellular organization and dynamics, as well as measure disease-linked changes. However, computational methods that can derive quantitative information from such massive datasets are currently lacking.

Studying the Dynamics of Chromatin-Binding Proteins in Mammalian Cells Using Single-Molecule Localization Microscopy.

Single-molecule localization microscopy (SMLM) allows the super-resolved imaging of proteins within mammalian nuclei at spatial resolutions comparable to that of a nucleosome itself (~20 nm). The technique is therefore well suited to the study of chromatin structure. Fixed-cell SMLM has already allowed temporal "snapshots" of how proteins are arranged on chromatin within mammalian nuclei.

Correction: Fast calcium transients in dendritic spines driven by extreme statistics.

[This corrects the article DOI: 10.1371/journal.pbio.

Adaptive Single-Channel EEG Artifact Removal With Applications to Clinical Monitoring.

Electroencephalography (EEG) has become very common in clinical practice due to its relatively low cost, ease of installation, non-invasiveness, and good temporal resolution. Portable EEG devices are increasingly popular in clinical monitoring applications such as sleep scoring or anesthesia monitoring. In these situations, for reasons of speed and simplicity only few electrodes are used and contamination of the EEG signal by artifacts is inevitable.

Emergence and fragmentation of the alpha-band driven by neuronal network dynamics.

Rhythmic neuronal network activity underlies brain oscillations. To investigate how connected neuronal networks contribute to the emergence of the α-band and to the regulation of Up and Down states, we study a model based on synaptic short-term depression-facilitation with afterhyperpolarization (AHP). We found that the α-band is generated by the network behavior near the attractor of the Up-state.

Nanoscale molecular architecture controls calcium diffusion and ER replenishment in dendritic spines.

Dendritic spines are critical components of neuronal synapses as they receive and transform synaptic inputs into a succession of calcium-regulated biochemical events. The spine apparatus (SA), an extension of smooth endoplasmic reticulum, regulates slow and fast calcium dynamics in spines. Calcium release events deplete SA calcium ion reservoir rapidly, yet the next cycle of signaling requires its replenishment.

Physics meets biology: The joining of two forces to further our understanding of cellular function.

Some biological questions are tough to solve through standard molecular and cell biological methods and naturally lend themselves to investigation by physical approaches. Below, a group of formally trained physicists discuss, among other things, how they apply physics to address biological questions and how physical approaches complement conventional biological approaches.

Chromatin stability generated by stochastic binding and unbinding of cross-linkers at looping sites revealed by Markov models.

Chromatin loops inside the nucleus can be stable for a very long time, which remains poorly understood. Such a time is crucial for chromatin organization maintenance and stability. We explore here several physical scenarios, where loop maintenance is due to diffusing cross-linkers (cohesin stabilized by two CTCF molecules) that can bind and unbind at the base of chromatin loops.

Triangulation Sensing to Determine the Gradient Source from Diffusing Particles to Small Cell Receptors.

How does a cell locate the source of molecular guidance cues from within a concentration gradient? We present a computational approach to recover the source from the absorbed fluxes at narrow receptor windows located on the surface of the cell. In the limit of fast binding, we solve the steady-state diffusion equation using an asymptotic approach and hybrid stochastic-analytical simulations. We show that the sensitivity to the gradient direction decays too rapidly to enable long-distance sensing.

Post-replicative pairing of sister ter regions in Escherichia coli involves multiple activities of MatP.

The ter region of the bacterial chromosome, where replication terminates, is the last to be segregated before cell division in Escherichia coli. Delayed segregation is controlled by the MatP protein, which binds to specific sites (matS) within ter, and interacts with other proteins such as ZapB. Here, we investigate the role of MatP by combining short-time mobility analyses of the ter locus with biochemical approaches.

Asymmetry Between Pre- and Postsynaptic Transient Nanodomains Shapes Neuronal Communication.

Synaptic transmission and plasticity are shaped by the dynamic reorganization of signaling molecules within pre- and postsynaptic compartments. The nanoscale organization of key effector molecules has been revealed by single-particle trajectory (SPT) methods. Interestingly, this nanoscale organization is highly heterogeneous.