Biology subjects

Comte, J.-C.

Publications and source records attributed to Comte, J.-C..

7 recordsLinked to original sources

bioRxiv2024

Induction of hemodynamic traveling waves by glial-related vasomotion in a rat model of neuroinflammation: implications for functional neuroimaging

BackgroundCerebral hemodynamics are crucial for brain homeostasis and serve as a key proxy for brain activity. Although this process involves coordinated interaction between vessels, neurons and glial cells, its dysregulation in neuroinflammation is not well understood. MethodsWe used in vivo mesoscopic functional ultrasound imaging to monitor cerebral blood volume changes during neuroinflammation in male rats injected with lipopolysaccharide (LPS) in the visual cortex, under resting-state or visual stimulation, combined to advanced ex vivo techniques for glial cell reactivity analysis. FindingsCortical neuroinflammation induced large oscillatory hemodynamic traveling waves in the frequency band of vasomotion ([~]0.1 Hz) in both anesthetized and awake rats. Vasomotor waves traveled through large distances between adjacent penetrating vessels, spanning the entire cortex thickness, and even extending to subcortical areas. Moreover, vasomotion amplitude correlated with microglial morphology changes and was significantly reduced by astrocytic toxins, suggesting that both microglia and astrocytes are involved in the enhancement of vasomotion during neuroinflammation. Notably, functional connectivity was increased under this oscillatory state and functional hyperemia was exacerbated. InterpretationThese findings reveal new spatiotemporal properties of cerebral vasomotion and suggest this is a major component of brain hemodynamics in pathological states. Moreover, reactive microglia and astrocytes are participating to increased vasomotion during neuroinflammation. For the field of functional neuroimaging, our results advocate for considering 0.1 Hz hemodynamic oscillations as an important complement to traditional measurements, particularly in neuroinflammatory conditions. Indeed, brain hemodynamics may provide insights not only into neuronal activity but also glial reactivity. FundingSupported by ANR ("LabCom-NI2D") and Auvergne-Rhone-Alpes Region ("BI2D").

neuroscience↗

bioRxiv2024

MorphoCellSorter: An Andrews plot-based sorting approach to rank microglia according to their morphological features

Microglia exhibit diverse morphologies reflecting environmental conditions, maturity or functional states. Thus, morphological characterization provides important information to understand microglial roles and functions. Most recent morphological analysis relies on classifying cells based on morphological parameters. However, this classification may lack biological relevance, as microglial morphologies represent a continuum rather than distinct, separate groups, and do not correspond to mathematically defined, clusters irrelevant of microglial cells function. Instead, we propose a new open-source tool, MorphoCellSorter, which assesses microglial morphology by automatically computing morphological criteria, using principal component analysis and Andrews plots to rank cells. MorphoCellSorter properly ranked cells from various microglia datasets in mice and rats of different age, from in vivo, in vitro and ex vivo models, that were acquired using diverse imaging techniques. This approach allowed for the discrimination of cell populations in various pathophysiological conditions. Finally, MorphoCellSorter offers a versatile, easy and ready-to-use method to evaluate microglial morphological diversity that could easily be generalized to standardize practices across laboratories.

neuroscience↗

bioRxiv2024

Contribution of the neuron-specific ATP1A3 to embryonic spinal circuit emergence

The early neurodevelopmental contributions of ion pumps remain poorly characterized. Combining analysis of public human embryo single-cell transcriptomic datasets and an embryonic chicken model, we found a conserved differentiation sequence whereby spinal cord neurons switch on neuron-specific alpha3 subunit (ATP1A3) of Na+/K+ ATPases. In the chicken model, ATP1A3 is distributed along axons and growth cones. Its knockdown alters axon pathfinding of dorsal interneurons (DIN) that wire spinocerebellar circuits. In mirror of reported electric field (EF)-driven cell migration, we found that DIN axons align in EFs, which was abolished by Na+/K+ ATPase inhibitor Ouabain and ATP1A3 knockdown. We recorded an embryonic trans-neural-epithelial potential generating EF whose pharmacological and surgical manipulation mimicked ATP1A3 knock-down-induced altered DIN axon pathfinding. Using DINs transplantation paradigm, we found that ATP1A3 is required cell-autonomously for EF-mediated long-range guidance. Finally, dominant-negative ATP1A3 mutation causing an early ATP1A3 childhood disease disrupts this fundamental developmental process, revealing unexpected pathogenic mechanisms.

developmental biology↗

bioRxiv2023

Synaptic strength dynamics at cortical synaptic pathways is encoded by vigilance states duration

Interactions among brain areas are essential to most cognitive functions. Neuronal interactions between these areas depend on the modulation of synaptic strength. However, this modulation remains poorly understood. We recorded evoked synaptic responses at four hippocampal pathways in freely moving male rats across 24 hours: the Perforant Path to Dentate Gyrus (PP-DG), Fornix to Prefrontal Cortex (Fx-PFC), Fornix to Nucleus Accumbens (Fx-NAc), and the Schaffer Collaterals to CA1 (SC-CA1). We preserved the temporal dynamics of vigilance states and synaptic responses and show for the first time that synaptic strength at these four hippocampal pathways oscillates, with a very slow periodicity. We demonstrate that synaptic strength at the PP-DG, Fx-PFC, Fx-NAc pathways show a positive correlation with the duration of active wakefulness (aWK) and a negative one with the duration of most sleep states (slow wave sleep (SWS) and rapid eye movement sleep (REM)), with a positive peak correlation time-lag of 1 to 10 minutes for aWK and SWS at these 3 pathways. In contrast, no significant correlation peak is found at the SC-CA1 pathway. Finally, a model based on hypnogram data and synaptic strength at the PP-DG pathway was able to predict the evolution of synaptic strength at the PP-DG, Fx-PFC and Fx-NAc pathways, but not at the SC-CA1 pathway. These results reveal that the temporal succession of vigilance states, particularly aWK and SWS, may contribute to memory processes through rapid modulation of synaptic strength at several pathways during the sleep-wakefulness cycle, suggesting that memory processes are not only dependent on sleep amount but also on sleep architecture.

neuroscience↗

bioRxiv2022

Upper limb rehabilitation after stroke: constraint versus intensive training. A longitudinal case-control study correlating motor performance with fMRI data

BackgroundThe reproducible beneficial effect of constraint-induced movement therapy (CIMT) in hemiparetic stroke patients makes it a good model to study brain plasticity during rehabilitation procedures. ObjectiveAssess the functional brain reorganization induced by each of the two components of CIMT: (i) non-affected upper-limb constraint and (ii) intensive training of the paretic arm. MethodsBrain activity of a right hemiparetic chronic stroke patient and of 10 healthy controls was recorded with a functional magnetic resonance imaging (fMRI) during a finger opposition task. For the patient, a total of 8 assessments were performed, before and after each component of CIMT. At each time point, brain activity during movement was compared with rest. Patients results were first compared to the control group and then correlated to motor performance across sessions. ResultsConstraint-therapy-related improvement was correlated with a decrease of cerebral activity in sensory-motor regions of both the affected and the non-affected hemispheres. Intensive-therapy-related improvement was correlated with the recruitment of pre-motor cortices and cerebellum in both hemispheres. ConclusionsTwo different patterns of brain activity underlie the effects of intensive training and constraint which could account for the respective effect of each component of the therapy.

neuroscience↗

bioRxiv2020

Working and Reference Memory tasks trigger opposed long-term synaptic changes in the rat dentate gyrus

Long-term storage of information into memory is supposed to rely on long-term synaptic plasticity processes. Detection of such synaptic changes after training in long-term or reference memory (RM) tasks has yet been scarce, variable and only studied on a short time scale. On the other hand, short-term or working memory (WM) is largely known to depend on persistent neuronal activity or short-term plasticity processes. However, processing information into WM could also involve long-term synaptic changes that could be responsible for the erasure/forgetting of items previously stored in WM playing the role of proactive interference. In order to study long-term synaptic changes associated with RM or WM, we trained chronically implanted rats in three different radial maze tasks: a classical RM task and two WM tasks involving different levels of proactive interference. Synaptic responses at the perforant path to dentate gyrus synapse were recorded on a long-time scale (24h) in freely-moving rats after training in one of these three tasks. We found that consolidation of long-term information leads to a delayed synaptic potentiation, occurring 9 hours after RM training and predicting good behavioral performance on the following day. In contrast, optimal information processing into WM triggers a synaptic depression immediately observed after training and lasting 3 hours, that could act as a mechanism for interference erasure/forgetting.

animal behavior and cognition↗

bioRxiv2018

Differential Recordings of Local Field Potential: A Genuine Tool to Quantify Functional Connectivity

Local field potential (LFP) recording is a very useful electrophysiological method to study brain processes. However, this method is criticized for recording low frequency activity in a large area of extracellular space potentially contaminated by distal activity. Here, we theoretically and experimentally compare ground-referenced (RR) with differential recordings (DR). We analyze electrical activity in the rat cortex with these two methods. Compared with RR, DR reveals the importance of local phasic oscillatory activities and their coherence between cortical areas. Finally, we show that DR provides a more faithful assessment of functional connectivity caused by an increase in the signal to noise ratio, and of the delay in the propagation of information between two cortical structures.

biophysics↗