Job ID: 118125

PhD project: Are spinal Cerebrospinal Fluid contacting neurons novel interoceptors involved in the modulation of supraspinal autonomic centers?

Position: Ph.D. Student

Deadline: 14 April 2024

Employment Start Date: 1 October 2024

Contract Length: 3 years

City: Marseille

Country: France

Institution: Aix-Marseille Université

Department: INT

Description:

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master’s degree in a non-French university. This project is one of the 13 proposed projects. Not all proposed projects will be funded, check our website for details.

State of art
Around the medullo-spinal central canal of most vertebrates, cerebrospinal fluid contacting neurons (CSF-cNs) are present. They exhibit a unique morphology with a single dendrite that project through the ependymal cell layer and ends in a protrusion bathed by the CSF. Their axons extend to the ventral region and form large bilateral fiber bundles, but in mammals little is known about the neuronal network they are inserted in. Further they selectively express “Polycystic Kidney Disease 2-like 1” channels (PKD2L1; members of the TRP superfamily) with properties of multimodal sensory receptors (temperature, pressure pH, osmolarity). Finally, they are thought to sense circulating bioactive molecules (hormones, neurotransmitters, cytokines, protons…) within the CSF.
Due to their localization, morphology, and physiological properties, CSF-cNs are suggested to act as sensory neurons and we hypothesize they represent novel actors of the interoceptive system to inform the CNS about its inner state. 

Objectives
Our recent results support this hypothesis and indicate that CSF-cNs send ascending projection to cholinergic neurons of the Dorsal Motor Nucleus of the Vagus nerve (DMV) a source of the parasympathetic innervation to several organs. The objective of the PhD project will be to characterize anatomical and functional CSF-cN connectivity within the DMV, test whether they are in turn modulated by supraspinal descending projection and understand at the behavioral level how CSF-cN contribution is integrated with other synaptic neuromodulatory systems to regulate physiological parameters. 

Methods
Tracing experiments in transgenic mouse lines combined with stereotactic viral-based injections will be performed with a focus on the above-mentioned circuits. Resolving CSF-cN connectivity maps by state-of-the-art conventional (confocal) and non-conventional (3D microscopy) imaging techniques with classical histology and whole tissue clearing. Testing the functional integration of the identified connectivity patterns with in vitro electrophysiology combined to optogenetics and behavioral tests. 

Expected results
Elucidating ascending and descending CSF-cN connectivity maps and the functional consequence on neuronal activity. Based on the results, we will demonstrate for the first time in mammals that CSF-cNs represent a novel actor of autonomous system informing the CNS about its inner state to trigger responses according to the individual needs (arousal, vigilance, attention, motivation, etc.). 

Feasibility
The SpiCCI team has all human resources, financial support, technical expertise and the required animal models/viral constructs to successfully conduct the proposed project. SpiCCI benefits from INT technical facilities. 

Expected candidate profile
– Highly motivated, implicated, and curious student with a background in cell biology and/or neuroscience. Capable of teamwork and adaptability. English speaking – Laboratory experience (histology and microscopy), proficient in basic IT. Capability in coding (Python, Matlab, Javascript) – The student will be enrolled in a caring environment and supervision and is expected to fully commit to his research and PhD project