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Role of neuroglial interactions in the cerebellar control of motor and cognitive functions

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General information

Reference : UMR9197-GLEDAL-001
Workplace : SACLAY
Date of publication : Monday, October 4, 2021
Scientific Responsible name : Glenn Dallérac
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 December 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

The cerebellum in a brain structure well-known for its role in the control of motor function. Yet, a growing body of clinical as well as experimental data point to its implication in cognitive functions. The cerbellem display a peculiar anatomical organisation, subdivided in distinct lobules that are connected, via the deep nuclei, to numerous motor and non-motor brain regions such as the prefrontal cortex, the ventral tegmental area and the hippocampus, thus providing anatomical basis for its influence on motor as well as cognitive aspects of behavior. Beyond the lobular organization, within each lobules clusters of cerebellar cortex neurons (Purkinje Cells, PC) are synchroneously activated such that functional microzones can be defined. Thus, the cerebellar contribution to motor and cognitive functions would occur through adaptation to multiple contingencies through selective activations of specific microzones. Interestingly, modeling studies suggesting a modular organization of the cerebellum through these microzones propose that the signal delineating these cerebellar microzones has been proposed to lie in the neuromodulatory aminergic inputs of the cerebellum. Yet, monoaminergic projections do not form synaptic specialization and operate through diffuse volume transmission, unlikely to suffice in defining specific microzones taking part in cognitive loops. Intriguingly, the cerebellum displays a unique form of highly specialized astroglia, the Bergmann glial cells (BGCs), closely interacting with Purkinje cells (PCs), the only neuronal output of the cerebellar cortex. They represent a major cell type of the cerebellar cortex, largely PCs and are well known for assisting neuronal activities by ensuring water, ions and glutamate homeostasis as well as metabolic support. Besides their role in these 'housekeeping' functions, BGCs have been found to control synaptic transmission, notably though modulation of synapse coverage. Our recent data show that the dense and finely meshed network provided by BGCs express the monoamine transporter VMAT2 and the monoamine (dopamine and noradrenaline) transporter DAT, an atypical feature in astroglial cells. We therefore hypothesize that through this unique property, BGCs modulate monoaminergic homeostasis in the cerebellar cortex allowing accurate delineation of microzones and control of motor and cognitive functions. The proposed thesis project thus aims at investigating the contribution of BGCs on the monoaminergic control of PC activities, and to which extent this participate in motor and cognitive processes.

Work Context

This research will be perfomed in the team of Glenn Dallérac at the Paris-Saclay Institute for Neurosciences. The PhD student will be supervised by Micaela Galante and Glenn Dallérac.

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