Biology subjects

Enger, R.

Publications and source records attributed to Enger, R..

6 recordsLinked to original sources

bioRxiv2025

Stretch and flow at the gliovascular interface: high-fidelity modelling of the mechanics of astrocyte endfeet

Astrocyte endfeet form a near-continuous sheath around the brains vasculature, defining the perivascular spaces (PVS) that are crucial for brain fluid flow and solute transport. Yet, their precise physiological role remains poorly understood. Using 3D electron microscopy data, we created a high-fidelity poroelastic computational model of an arteriole segment with surrounding endfeet and parenchyma to investigate tissue displacement and fluid flow within the PVS, endfeet, and extracellular space (ECS) in response to blood vessel pulsations. Our model predicts that arteriole dilations compress the PVS while expanding the overall endfoot sheath volume due to tangential stretch. Moreover, fluid exchange primarily occurs through inter-endfoot gaps, driven by pressure differences, rather than across the aquaporin-4 (AQP4) rich endfoot membrane. PVS stiffness critically modulates these dynamics: increased stiffness of the PVS, for instance, due to vessel pathology or aging, would minimize or even reverse fluid exchange at the gliovascular interface. While AQP4 mediated water movement has a negligible impact on pulsation-driven mechanics, it significantly enhances osmotically driven fluid flow. Overall, our findings elucidate the complex balance of forces governing gliovascular mechanics and suggest that PVS composition strongly influences endfoot-parenchymal fluid exchange. SignificancePerivascular spaces, formed by astrocyte endfeet wrapping the vasculature, are high-conduit pathways for brain fluid flow and clearance. Vascular pulsations drive this flow, but the resulting mechanical interactions at the gliovascular interface remain largely unknown. We introduce a computational model of the solid and fluid mechanics here, using realistic geometries to capture intricate astrocyte morphology at the subcellular level. Our simulations reveal that changes in perivascular composition - associated with aging or neurodegenerative diseases - fundamentally alter mechanical coupling, potentially impeding fluid transport. This work provides a mechanistic framework for understanding brain clearance and constitutes a foundational model for computational studies of mechanical forces in the nervous system.

neuroscience↗

bioRxiv2022

Sleep cycle-dependent vascular dynamics enhance perivascular cerebrospinal fluid flow and solute transport

Perivascular spaces (PVS) are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. Using two-photon imaging of naturally sleeping mice we demonstrate sleep cycle-dependent PVS dynamics - slow, large-amplitude oscillations in NREM, a reduction in REM and an enlargement upon awakening at the end of a sleep cycle. By biomechanical modeling we demonstrate that these sleep cycle-dependent PVS dynamics drive fluid flow and solute transport.

neuroscience↗

bioRxiv2021

Validating a computational framework for ionicelectrodiffusion with cortical spreading depression as a case study

Cortical spreading depression (CSD) is a wave of pronounced depolarization of brain tissue accompanied by substantial shifts in ionic concentrations and cellular swelling. Here, we validate a computational framework for modelling electrical potentials, ionic movement, and cellular swelling in brain tissue during CSD. We consider different model variations representing wild type or knock-out/knock-down mice and systematically compare the numerical results with reports from a selection of experimental studies. We find that the data for several CSD hallmarks obtained computationally, including wave propagation speed, direct current shift duration, peak in extracellular K+ concentration as well as a pronounced shrinkage of extracellular space, are well in line with what has previously been observed experimentally. Further, we assess how key model parameters including cellular diffusivity, structural ratios, membrane water and/or K+ permeabilities affect the set of CSD characteristics. Significance StatementMovement of ions and molecules in and between cellular compartments is fundamental for brain function. Cortical spreading depression (CSD) is associated with dramatic failure of brain ion homeostasis. Better understanding the sequence of events in CSD could thus provide new insight into physiological processes in the brain. Despite extensive experimental research over the last decades, even basic questions related to mechanisms underlying CSD remain unanswered. Computational modelling can play an important role going forward, since simulation studies can address hypotheses that are difficult to target experimentally. Here, we assess the physiological validity of a novel mathematical framework for detailed modelling of brain electrodiffusion and osmosis - and provide a platform for in silico studies of CSD and other cerebral electro-mechanical phenomena.

neuroscience↗

bioRxiv2021

Impaired astrocytic Ca2+ signalling in awake Alzheimer's disease transgenic mice

Increased astrocytic Ca2+ signaling related to amyloid plaques has been shown in Alzheimers disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signalling in such mice without the confounding effects of anesthesia. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signalling in 15-months old plaque-bearing mice. This points to a potential decoupling of neuromodulatory activation and astrocytic Ca2+ activity, which may account for some of the cognitive dysfunctions observed in Alzheimers disease.

neuroscience↗

bioRxiv2020

RippleNet: A Recurrent Neural Network for Sharp Wave Ripple (SPW-R) Detection

Hippocampal sharp wave ripples (SPW-R) have been identified as key bio-markers of important brain functions such as memory consolidation and decision making. SPW-R detection typically relies on hand-crafted feature extraction, and laborious manual curation is often required. In this multidisciplinary study, we propose a novel, self-improving artificial intelligence (AI) method in the form of deep Recurrent Neural Networks (RNN) with Long Short-Term memory (LSTM) layers that can learn features of SPW-R events from raw, labeled input data. The algorithm is trained using supervised learning on hand-curated data sets with SPW-R events. The input to the algorithm is the local field potential (LFP), the low-frequency part of extracellularly recorded electric potentials from the CA1 region of the hippocampus. The output prediction can be interpreted as the time-varying probability of SPW-R events for the duration of the input. A simple thresholding applied to the output probabilities is found to identify times of events with high precision. The reference implementation of the algorithm, named RippleNet, is open source, freely available, and implemented using a common open-source framework for neural networks (tensorflow.keras) and can be easily incorporated into existing data analysis workflows for processing experimental data.

neuroscience↗

bioRxiv2019

Ca2+ signaling in astrocytes is sleep-wake state specific and modulates sleep

Astrocytic Ca2+ signaling has been intensively studied in health and disease but remains uncharacterized in sleep. Here, we employed a novel activity-based algorithm to assess astrocytic Ca2+ signals in the barrel cortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We discovered that Ca2+ signaling in astrocytes exhibits distinct features across the sleep-wake cycle and is reduced in sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow-wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Genetic ablation of a key astrocytic Ca2+ signaling pathway resulted in fragmentation of slow-wave sleep, yet increased the frequency of sleep spindles. Our findings suggest a role for astrocytic Ca2+ signaling in modulating sleep.

neuroscience↗