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Ferrier, J.

Publications and source records attributed to Ferrier, J..

5 recordsLinked to original sources

Temporal Patterns of Brain Network Plasticity During the Onset and Maintenance of Neuropathic Pain in Male Mice

Neuropathic pain arises from complex peripheral and central mechanisms and induces long-lasting maladaptive changes in the brain. To investigate the temporal dynamics of these changes, we examined resting-state functional connectivity (FC) in a mouse model of neuropathic pain across its initiation and maintenance phases. Using functional ultrasound imaging to capture whole-brain FC over disease progression, we conducted two complementary studies: a longitudinal assessment in anesthetized animals and an analysis of awake cohorts at distinct disease stages. Both exploratory and literature-guided analyses revealed that FC across most large-scale networks remained remarkably stable during pain maintenance. In contrast, pain onset was marked by enhanced FC between key regions involved in sensory, emotional, and motivational processing, including the motor cortex and nucleus accumbens, the prelimbic and insular cortices, and the infralimbic cortex and hypothalamus. As pain persisted, we observed reduced FC within the somatomotor network, reflecting functional disconnection. Additionally, postsurgical pain alone produced enduring FC changes within the prefrontal cortex, hippocampus, and insula, indicating long-term central plasticity independent of neuropathic injury. Together, these findings reveal dynamic, network-specific adaptations that distinguish the onset and maintenance phases of neuropathic pain and surgery-related plasticity.

neuroscience↗

In vivo microvascular flow quantification in the mouse brain using Row-Column Ultrasound Localization Microscopy and directed graph analysis

Brain perfusion relies on a complex vascular network of arteries, veins, and capillaries to meet its constant demand for oxygen and nutrients. Disruption of this microvascular system is a hallmark of many neurological disorders, including small vessel disease, stroke, and brain tumors. As such, high-resolution in vivo imaging of cerebral microvascular flow and structure remains critical to understanding these pathologies. Among them, Ultrasound Localization Microscopy (ULM) allows noninvasive imaging of microvascular network at subwavelength resolution using injected microbubbles, but the approach remains mainly limited to 2D imaging with few volumetric implementations. In this study, we explore in vivo transcranial 3D ULM of the mouse brain using Row-Column Arrays (RCA) and introduce an analysis framework to build a flow-directed vascular graph from the ULM microbubble tracking data, allowing to differentiate between subgraphs of artery-like and vein-like vascular segments. Combined with Allen-based and Radius-based segmentations, we extract metrics including cerebral blood flow (CBF), microbubble (MB) velocity, flowrate, CBV fraction, vascular segment length and tortuosity in sixty-six different vascular classes. This high-sensitivity framework enables in vivo microvascular imaging and quantification in mice and provides a scalable platform for preclinical neurovascular studies in health and disease.

bioengineering↗

Speed Vascular Patterns in the Spatial Navigation System

The hippocampal formation is central to spatial navigation, hosting neurons that encode position, direction, and speed. Yet, the brain-wide vascular dynamics supporting these processes remain poorly understood, especially during naturalistic behaviors. Here, we adapted functional ultrasound (fUS) imaging to examine how cerebral blood volume (CBV) changes relate to behavioral parameters in freely moving rats. High-resolution imaging of hippocampal-parahippocampal regions during open-field exploration reveals strong correlations between CBV dynamics and animal speed, with distinct regional activation patterns and temporal delays. Lagged general linear modeling uncovers information flow from the thalamus to parahippocampal regions, including the medial entorhinal cortex, and to hippocampal subfields (dentate gyrus, CA1-CA3), consistent with a hierarchical processing framework. The analysis also links CBV with angular head speed and the dorsal thalamus. Decoding analyses show that CBV signals not only encode speed precisely but also capture spatial features like proximity to walls and corners, even when univariate analyses do not. This decoding remains robust across animals, underscoring the universality of speed encoding in vascular dynamics. We also identify slow CBV oscillations in the hippocampus aligned with minute-scale speed fluctuations, suggesting a neurovascular signature of exploratory behavior. These findings reveal a hemodynamic signature of speed representation in the navigation system, arising from energy demands in a continuous attractor network model for path integration, where population activity and synaptic currents increase quadratically with animal speed as both peak firing rates and neuronal recruitment scale linearly with animal speed. Moreover, they highlight functional ultrasound imaging as a powerful approach for probing the hemodynamic basis of navigation.

neuroscience↗

Active Notch Signaling is Required for Arm Regeneration in a Brittle Star

Cell signaling pathways play vital roles in coordinating cellular events in development. For example, the Notch signaling pathway is highly conserved across all multicellular animals and is known to coordinate a multitude of diverse cellular events, including proliferation, differentiation, fate specification, and cell death. Specific functions of the pathway are, however, highly context-dependent and are not well characterized in post-traumatic regeneration. Here, we use a small-molecule inhibitor of the pathway (DAPT) to demonstrate that Notch signaling is required for proper arm regeneration in the brittle star Ophioderma brevispina, a highly regenerative member of the phylum Echinodermata. We also employ a transcriptome-wide gene expression analysis to characterize the downstream genes controlled by the Notch pathway in the brittle star regeneration. We demonstrate that arm regeneration involves an extensive crosstalk between the Notch pathway and other cell signaling pathways. In the regrowing arm, Notch regulates the composition of the extracellular matrix, cell migration, proliferation, and apoptosis, as well as components of the innate immune response. We also show for the first time that Notch signaling regulates the activity of several transposable elements. Our data also suggests that one of the possible mechanisms through which Notch sustains its activity in the regenerating tissues is via suppression of Neuralized1.

developmental biology↗

A robotic platform for fluidically-linked human body-on-chips experimentation

Here we describe of an Interrogator instrument that uses liquid-handling robotics, a custom software package, and an integrated mobile microscope to enable automated culture, perfusion, medium addition, fluidic linking, sample collection, and in situ microscopic imaging of up to 10 Organ Chips inside a standard tissue culture incubator. The automated Interrogator platform maintained the viability and organ-specific functions of 8 different vascularized, 2-channel, Organ Chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier (BBB), and brain) for 3 weeks in culture when fluidically coupled through their endothelium-lined vascular channels using a common blood substitute medium. When an inulin tracer was perfused through the multi-organ Human Body-on-Chips (HuBoC) fluidic network, quantitative distributions of this tracer could be accurately predicted using a physiologically-based multi-compartmental reduced order (MCRO) in silico model of the experimental system derived from first principles. This automated culture platform enables non-invasive imaging of cells within human Organ Chips and repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling, which should facilitate future HuBoc studies and pharmacokinetics (PK) analysis in vitro.

bioengineering↗