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Mechanisms by which astrocytes gate tactile input to nociceptive neurons

ABG-124637 Thesis topic
2024-06-15 Other public funding
INSERM/Universite Clermont Auvergne
- Auvergne-Rhône-Alpes - France
Mechanisms by which astrocytes gate tactile input to nociceptive neurons
  • Biology
  • Psychology, neurosciences
Pain, Disinhibition Astrocyte, GABA, Glycine, Parvalbumin

Topic description

We and others have shown that peripheral injuries induces disinhibition in the dorsal horn, which unmasks tactile inputs to superficial projection neurons that normally respond exclusively to noxious input, thus sustaining mechanical hypersensitivity. A recent study demonstrated that transient optogenetic stimulation of spinal astrocytes could produce mechanical allodynia in naïve rats indicating that astrocyte activation is sufficient to drive the induction of pain. Therefore, the aim of this project is to explore the circuits by which astrocyte leads to mechanical hypersensitivity. The question will be investigated through a combination of state of the art approaches, such as virally tool, systematic transcriptomic analysis and 2-photon calcium imaging, completed by electrophysiological, morphological, biochemical, molecular, pharmacological, and behavioral complementary technique

Publications en rapport avec le projet :

- Descheemaeker A, Poras H, Wurm M, Luccarini P, Ouimet T, Dallel R. Dual enkephalinase Inhibitor PL37 as a potential novel treatment of migraine: evidence from a rat model. Brain 2022, 145:2664-2670.

- Signoret-Genest J, Barnet M, Gabrielli F, Aissouni Y, Artola A, Dallel R, Antri M, Tovote P, - Monconduit L Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus. J Headache Pain. 2023 Dec 8;24(1):165.

- El Khoueiry C, Alba-Delgado C, Antri M, Gutierrez-Mecinas M, Todd AJ, Artola A, Dallel R.GABAA and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina IIi PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization. Cells. 2022 Apr 15;11(8):1356

- Cantaut-Belarif Y, Antri M, Pizzarelli R, Colasse S, Vaccari I, Soares S, Renner M, Dallel R, Triller A, Bessis A. Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord.  J Cell Biol. 2017 Sep 4;216(9):2979-2989.

- Miraucourt LS, Peirs C, Dallel R, Voisin DL Glycine inhibitory dysfunction turns touch into pain through astrocyte-derived D-serine. Pain. 2011 Jun;152(6):1340-1348

Starting date

2024-10-01

Funding category

Other public funding

Funding further details

IDEX/I-Site

Presentation of host institution and host laboratory

INSERM/Universite Clermont Auvergne

Neuro-Dol brings together clinicians (odontologists, anesthetists, neurologists and psychologists) and neurobiologists to carry out research from the cellular to the human level. Our aim is to elucidate the pathophysiological mechanisms of chronic pain. The laboratory has both large (~800 m2) and modern premises, which make it possible to welcome new researchers and teacher-researchers and to develop new technological approaches. All the fundamental themes are tackled in a multidisciplinary way, combining the most modern neuroscience techniques.

The team consists of 40 people and uses several approaches (electrophysiological, behavioral, morphological, molecular…) to study the pathophysiology of chronic pain. The laboratory has 2 electrophysiology stations for multi-unit, multi-site extracellular in vivo recordings and 3 ex vivo electrophysiology stations (patch clamp) and several microscopes including 1 multiphoton. It also has an immunohistochemistry and molecular biology facility. For studies in awake animals, the laboratory is equipped with systems for the analysis of neurovegetative parameters (telemetry), in vivo calcium imaging and optogenetics (Inscopix) and behavioural parameters (videography, Noldus, etc.).

PhD title

Doctorat en Neurosciences

Country where you obtained your PhD

France

Institution awarding doctoral degree

UNIVERSITE CLERMONT AUVERGNE

Graduate school

Sciences de la vie, Santé, Agronomie, Environnement

Candidate's profile

 

The candidate must have a Master's degree in neuroscience. It is an advantage if the candidate has already used electrophysiological techniques, behavioural analysis and/or viral injections during their Master's degree.

 

To be eligible to apply to the doctoral school, the candidate must be in the top half of their Master's class and have an average grade of at least 12 out of 20.

2024-09-16
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