Functional contribution of the mesencephalic locomotor region to locomotion

Authors: Josset, Nicolas
Advisor: Bretzner, Frédéric
Abstract: Because it is natural and easy to walk, it could seem that this act is produced as easily as it is accomplished. On the contrary, locomotion requires an intricate and complex neural interaction between the supraspinal, spinal and peripheric neurons to obtain a locomotion that is smooth and adapted to the environment. The Mesencephalic Locomotor Region (MLR) is a supraspinal brainstem locomotor center that has the particular role of initiating locomotion and inducing a transition between locomotor gaits. However, although this region was initially identified as the cuneiform nucleus (CnF), a cluster of glutamatergic neurons, and the pedunculopontine nucleus (PPN), a cluster of glutamatergic and cholinergic neurons, its anatomical correlate is still a matter of debate. And while it is proven that, either under MLR stimulation or in order to increase locomotor speed, most quadrupeds exhibit a wide range of locomotor gaits from walk, to trot, to gallop, the exact range of locomotor gaits in the mouse is still unknown. Here, using kinematic analysis we first decided to identify to assess locomotor gaits C57BL/6 mice. Based on the symmetry of the gait and the inter-limb coupling, we identified and characterized 8 gaits during locomotion displayed through a continuum of locomotor frequencies, ranging from walk to trot and then to gallop with various sub-types of gaits at the slowest and highest speeds that appeared as attractors or transitional gaits. Using graph analysis, we also demonstrated that transitions between gaits were not random but entirely predictable. Then we decided to analyze and characterize the functional contributions of the CnF and PPN’s neuronal populations to locomotor control. Using transgenic mice expressing opsin in either glutamatergic (Glut) or cholinergic (CHAT) neurons, we photostimulated (or photoinhibited) glutamatergic neurons of the CnF or PPN or cholinergic neurons of the PPN. We discovered that glutamatergic CnF neurons initiate and modulate the locomotor pattern, and accelerate the rhythm, while glutamatergic and cholinergic PPN neurons decelerate it. By initiating, modulating, and accelerating locomotion, our study identifies and characterizes distinct neuronal populations of the MLR. Describing and defining thoroughly the MLR seems all the more urgent since it has recently become a target for spinal cord injury and Parkinson’s disease treatment.
Document Type: Thèse de doctorat
Issue Date: 2018
Open Access Date: 25 July 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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