Biology subjects

Girard, D.

Publications and source records attributed to Girard, D..

5 recordsLinked to original sources

bioRxiv2025

Notch canonical activity in a subset of glial cells regulates short-term memory in Drosophila

Notch is a transmembrane receptor expressed at the cell surface that mediates transcriptional responses upon binding to its ligands, in a variety of contexts. Evolutionarily conserved, Notch plays a key role in numerous cell fate decisions during development and is also required in post-mitotic brain neurons for the consolidation of long-term memory and long-term habituation. Notch signaling is highly expressed in glial cells, where it plays a key role in regulating their development and proliferation. More recently, a Notch-dependent neuroglial pathway has been implicated in modulating the susceptibility of short-term memory to sleep deprivation in Drosophila. In this study, we demonstrate that canonical Notch signaling in glia-- mediated by the Delta ligand and the transcription factor Suppressor of Hairless--is activated in a subset of cortex and ensheathing glial cells. This signaling is essential for the formation of short-term memory in the aversive phototaxic suppression assay, which is sensitive to sleep deprivation. Dopaminergic transmission is known to be required for this type of learning and is negatively impacted by sleep deprivation, suggesting a possible interaction between Notch and dopamine pathways. Supporting this idea, we find that modulating dopaminergic transmission downregulates canonical Notch activity in glial cells. Conversely, activating Notch signaling in glia near dopaminergic neurons prevents the learning impairments typically caused by sleep deprivation. Notably, Notch signaling itself does not appear to alter dopamine levels in the brain. Together, these findings indicate that canonical Notch signaling in a specific subset of glial cells is essential for short-term memory formation and is modulated by dopaminergic signaling. This suggests that sleep loss-induced disruption of dopaminergic transmission impairs learning by downregulating canonical Notch signaling. Since Notch homologs are highly expressed in mammalian glia, this pathway may be conserved and functionally relevant in other species, including humans.

neuroscience↗

bioRxiv2024

Dye-based Fluorescent Organic Nanoparticles, New Promising Tools for Optogenetics

Dye-based fluorescent organic nanoparticles are a specific class of nanoparticles obtained by nanoprecipitation in water of pure dyes only. While the photophysical and colloidal properties of the nanoparticles strongly depend on the nature of the aggregated dyes, their excellent brightness in the visible and in the near infrared make these nanoparticles a unique and versatile platform for in vivo application. This article examines the promising utilization of these nanoparticles for in vivo optogenetics applications. Their photophysical properties as well as their biocompatibility and their capacity to activate Chrimson opsin in vivo through fluorescence reabsorption process are demonstrated. Additionally, an illustrative example of employing these nanoparticles in fear reduction in mice through close-loop stimulation is presented. Through an optogenetic methodology, the nanoparticles demonstrate an ability to selectively manipulate neurons implicated in the fear response and diminish the latter. Dye-based fluorescent organic nanoparticles represent a promising and innovative strategy for optogenetic applications, holding substantial potential in the domain of translational neuroscience. This work paves the way for novel therapeutic modalities for neurological and neuropsychiatric disorders.

neuroscience↗

bioRxiv2022

Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior

In threatening situations, animals exhibit a broad range of behavioral and autonomic responses. As such, a crucial adaptive response is the inhibition of pain, which facilitates relevant defensive behaviors that promote survival. Whereas the structures and mechanisms involved in fear and pain behaviors are well documented, little is known about the precise neuronal mechanisms mediating the emotional regulation of endogenous pain-suppression. Here, we used a combination of behavioral, anatomical, optogenetic, and electrophysiological approaches to investigate, in male mice, the role of somatostatin-expressing cells in the ventrolateral periaqueductal gray matter (SST+ vlPAG cells) in the control of analgesia induced during defensive states. Our data indicate that optogenetic inhibition of SST+ vlPAG cells promotes analgesia irrespective of animal defensive state. In contrast, optogenetic activation of long-range SST+ vlPAG cells that project to the rostral ventromedial medulla (RVM) abolishes the analgesia mediated by fear behavior. Together, these results identify a novel circuit mechanism composed of long-range SST+ vlPAG cells projecting to the RVM that regulate analgesia elicited during defensive states.

neuroscience↗

bioRxiv2021

Spinal cord injury reprograms muscle fibro-adipogenic progenitors to formheterotopic bones within muscles

The cells-of-origin of neurogenic heterotopic ossifications (NHO), which develop frequently in the periarticular muscles following spinal cord injuries (SCI) and traumatic brain injuries, remain unclear because the skeletal muscle harbors two progenitor cell populations: satellite cells (SCs) which are myogenic, and fibro-adipogenic progenitors (FAPs) which are mesenchymal. Lineage-tracing experiments using the Cre recombinase /LoxP system were performed in two mouse strains with the fluorescent protein ZsGreen specifically expressed in either SCs or FAPs in the skeletal muscles under the control of the Pax7 or Prrx1 gene promotors respectively. These experiments demonstrate that following a muscle injury, SCI causes the upregulation of PDGFR on FAPs but not SCs and the failure of SCs to regenerate myofibers in the injured muscle, with instead reduced apoptosis and continued proliferation of muscle resident FAPs enabling their osteogenic differentiation into NHO. No cells expressing ZsGreen under the Prrx1 promoter were detected in the blood after injury suggesting that the cells-of-origin of NHO are locally derived from the injured muscle. We validated these findings in the human pathology using human NHO biopsies. PDGFR+ mesenchymal cells isolated from the muscle surrounding NHO biopsies could develop ectopic human bones when transplanted into immunocompromised mice whereas CD56+ myogenic cells had a much lower potential. Therefore, NHO is a pathology of the injured muscle in which SCI reprograms FAPs to uncontrolled proliferation and differentiation into osteoblasts.

pathology↗

bioRxiv2021

Interleukin-1 is overexpressed in injured muscles following spinal cord injury and promotes neurogenic heterotopic ossification

Neurogenic heterotopic ossifications (NHOs) form in periarticular muscles following severe spinal cord (SCI) and traumatic brain injuries. The pathogenesis of NHO is poorly understood with no effective preventive treatment. The only curative treatment remains surgical resection of pathological NHOs. In a mouse model of SCI-induced NHO that involves a transection of the spinal cord combined with a muscle injury, a differential gene expression analysis revealed that genes involved in inflammation such as interleukin-1{beta} (IL-1{beta}) were overexpressed in muscles developing NHO. Using mice knocked-out for the gene encoding IL-1 receptor (IL1R1) and neutralizing antibodies for IL-1 and IL-1{beta}, we show that IL-1 signaling contributes to NHO development following SCI in mice. Interestingly, other proteins involved in inflammation that were also overexpressed in muscles developing NHO, such as colony-stimulating factor-1, tumor necrosis factor or C-C chemokine ligand-2 did not promote NHO development. Finally using NHO biopsies from SCI and TBI patients, we show that IL-1{beta} is expressed by CD68+ macrophages. IL-1 and IL-1{beta} produced by activated human monocytes promote calcium mineralization of fibro-adipogenic progenitors isolated from muscles surrounding NHOs. Altogether these data suggest that interleukin-1 promotes NHO development in both humans and mice.

physiology↗