Biology subjects

Delmas, P.

Publications and source records attributed to Delmas, P..

5 recordsLinked to original sources

bioRxiv2025

The Brain/MINDS 3D Digital Marmoset Brain Atlas Version 2.0: Population-based Cortical Region Parcellations with Multi-Modal Standard Templates

We present our new Brain/MINDS 3D digital marmoset brain atlas version 2.0 (BMA2.0), a population-based 3D digital brain atlas of the common marmoset (Callithrix jacchus), designed to overcome the limitations of previous single subject atlases that are prone to structural biases arising from individual variation. Here, manually delineated cortical regions from 10 myelin-stained brains were used to create a generalized cortical parcellation. Newly refined subcortical regions from a previous atlas and a completely new cerebellum parcellation were also incorporated, resulting in a comprehensive whole brain parcellation for both hemispheres. To facilitate multimodal data analysis, the atlas package includes co-registered average templates for myelin and Nissl staining from the same individuals, ex vivo MRI T2 (91 individuals), and in vivo MRI T2 (446 individuals). Cortical flat maps and pial, cortical mid-thickness, and white matter surfaces are also provided. BMA2.0 provides a central brain space for multimodal data integration, spatial analysis, and comparative neuroscience. Standard formats and transformations are provided for easy integration into existing workflows and interoperability with existing atlases.

neuroscience↗

bioRxiv2023

D-Serine agonism of GluN1-GluN3 NMDA receptors regulates the activity of enteric neurons and coordinates gut motility

The enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the expression of ionotropic glutamate receptors in the ENS, their roles in the gut remain elusive. Here, by using an array of immunohistochemistry, molecular profiling and functional assays, we uncover a new role for D-serine (D-Ser) and non-conventional GluN1-GluN3 N-methyl D-aspartate receptors (NMDARs) in regulating ENS functions. We demonstrate that D-Ser is produced by serine racemase (SR) expressed in enteric neurons. By using both in situ patch clamp recording and calcium imaging, we show that D-Ser alone acts as an excitatory neurotransmitter in the ENS independently of the conventional GluN1-GluN2 NMDARs. Instead, D-Ser directly gates the non-conventional GluN1-GluN3 NMDARs in enteric neurons from both mouse and guinea-pig. Pharmacological inhibition or potentiation of GluN1-GluN3 NMDARs had opposite effects on mouse colonic motor activities, while genetically driven loss of SR impairs gut transit and fluid content of pellet output. Our results demonstrate the existence of native GluN1-GluN3 NMDARs in enteric neurons and open new perspectives on the exploration of excitatory D-Ser receptors in gut function and diseases.

neuroscience↗

bioRxiv2023

FLT3 signaling inhibition preserves opioid analgesia while abrogating tolerance and hyperalgesia

Opioid analgesia is counteracted on chronic use by tolerance and hyperalgesia inducing dose escalation and life-threatening overdoses. Mu opiate receptors (MOR) expressed in primary sensory neurons were recently found to control tolerance and hyperalgesia, but the underlying mechanisms remained elusive. Here we show that genetic inactivation of fms-like tyrosine kinase receptor 3 (FLT3) receptor in sensory neurons abrogates morphine tolerance and hyperalgesia by preventing MOR-induced hyperactivation of the cAMP signaling pathway and subsequent excitatory adaptive processes. Moreover, the specific FLT3 inhibitor BDT001 potentiates morphine analgesia in acute and chronic pain models, without aggravating morphine adverse effects, and reverses tolerance and hyperalgesia once installed. Thus, FLT3 appears as a key regulator of the MOR signaling pathway and its pharmacological blockade shows promise to enhance chronic opioid analgesic efficacy.

neuroscience↗

bioRxiv2021

Patch-seq of mouse DRG neurons reveals candidate genes for specific mechanosensory functions

A variety of mechanosensory neurons are involved in touch, proprioception and pain. Many molecular components of the mechanotransduction machinery subserving these sensory modalities remain to be discovered. Here, we combined recordings of mechanosensitive (MS) currents in mechanosensory neurons with single cell RNA sequencing. In silico combined analysis with a large-scale dataset enables assigning each transcriptome to DRG genetic clusters. Correlation of current signatures with single-cell transcriptomes provides a one-to-one correspondence between mechanoelectric properties and transcriptomically-defined neuronal populations. Moreover, gene expression differential comparison provides a set of candidate genes for mechanotransduction complexes. Piezo2 was expectedly found to be enriched in rapidly adapting MS current-expressing neurons, whereas Tmem120a and Tmem150c, thought to mediate slow-type MS currents, were uniformly expressed in all neuron subtypes, irrespective of their mechano-phenotype. Further knock-down experiments disqualified them as mediating DRG MS currents. This dataset constitutes an open-resource to explore further the cell-type-specific determinants of mechanosensory properties.

neuroscience↗

bioRxiv2018

Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature

Flow of cerebrospinal fluid (CSF) may contribute to spine morphogenesis, as mutations affecting both cilia motility and CSF flow lead to scoliosis1. However, the mechanisms underlying detection of the CSF flow in the central canal of the spinal cord remain elusive. Here we used full-field optical coherence tomography (FF-OCT) and bead tracking to demonstrate that CSF flows bidirectionally along the antero-posterior axis in the central canal of zebrafish embryos. In the zebrafish mutant cfap298tm304, previously known as kurly, reduction of cilia motility slows transport down the length of central canal. To investigate downstream mechanisms that could transduce CSF flow, we performed calcium imaging in sensory neurons contacting the CSF (CSF-cNs) and found that disruption in cilia motility impaired the activity of CSF-cNs. CSF-cNs across species express the transient receptor potential channel PKD2L1, also known as TRPP3, which contributes to CSF-cN chemosensory properties. Using calcium imaging and whole-cell patch clamp recordings, we found that the loss of the Pkd2l1 channel in pkd2l1 mutant embryos also abolished CSF-cN activity. Whole-cell recordings further demonstrated that opening of a single channel is sufficient to trigger action potentials in wild type CSF-cNs. Recording from isolated cells in vitro, we showed that CSF-cNs are mechanosensory cells that respond to pressure in a Pkd2l1-dependent manner. Interestingly, adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, reminiscent of kyphosis in humans. Our study indicates that CSF-cNs are mechanosensory cells whose spontaneous activity reflects CSF flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to the maintenance of the natural curvature of the spine.

neuroscience↗