1. The supraspinal control of locomotion - Goal-directed locomotion and locomotor centres
This aspect of the research in the lab is aimed at gaining a better understanding of the cellular mechanisms underlying the supraspinal control of locomotion in vertebrates. We examine how sensory inputs initiate locomotor activity in a lower vertebrate, the lamprey. We also seek to identify the role of different regions of the central nervous system involved in the control and initiation of locomotion. Supraspinal locomotor regions play a key role in goal-directed locomotion where internal cues provide the triggering signal of locomotion. We also examine the mechanisms by which locomotion is initiated and controlled by external sensory inputs as well as by internal cues related to basic biological functions such as feeding, exploration, and reproduction. Because the general anatomical and physiological organization of the central nervous system is highly conserved between different species of vertebrates, information gained in lampreys will provide useful knowledge applicable to other vertebrates, including humans.
This aspect of the research in the lab is aimed at gaining a better understanding of the cellular mechanisms underlying the supraspinal control of locomotion in vertebrates. We examine how sensory inputs initiate locomotor activity in a lower vertebrate, the lamprey. We also seek to identify the role of different regions of the central nervous system involved in the control and initiation of locomotion. Supraspinal locomotor regions play a key role in goal-directed locomotion where internal cues provide the triggering signal of locomotion. We also examine the mechanisms by which locomotion is initiated and controlled by external sensory inputs as well as by internal cues related to basic biological functions such as feeding, exploration, and reproduction. Because the general anatomical and physiological organization of the central nervous system is highly conserved between different species of vertebrates, information gained in lampreys will provide useful knowledge applicable to other vertebrates, including humans.
Goal-directed locomotion and locomotor centers
Goal-directed locomotion requires the activation of genetically defined neuronal networks in the spinal cord and the brain. Whereas the neural networks in the spinal cord are responsible for generating the basic locomotor synergy, the neural networks involved in initiating and modifying locomotor activity with respect to environmental conditions are located above the spinal cord. One such locomotor control center is located in the mesencephalon and has been named the Mesencephalic Locomotor Region (MLR). This region was first discovered in mammals and later found in all vertebrate species investigated. What most remarkable about this region is that it not only induces locomotion but also controls its intensity somewhat like a rheostat. What is yet not understood is the cellular mechanisms by which this is achieved. To analyze this problem at a cellular level, the lamprey model is more favourable than higher vertebrates due to its relative simplicity.
We take advantage of this model to investigate how the MLR activates brainstem reticulospinal cells to elicit locomotion. For example we have identified:
The recruitment patterns of reticulospinal cells to MLR stimulation
We have recently identified different populations of reticulospinal neurons in the brainstem according to their pattern of activity during locomotion elicited by MLR stimulation. One population of cells was activated at the beginning of locomotion, another one was activated throughout the locomotor bout, and a third population was activated both at the beginning and at the end of the locomotor bout. Several lines of evidence collected during our studies indicate that the latter population is involved in stopping locomotion. We are now pursuing research to characterize the inputs and the targets of the different populations of reticulospinal neurons involved in the control of locomotion.
The anatomical connections involved, and the role of the different neurotransmitters
This information is fundamental for our comprehension of how the nervous system initiates and controls locomotor behavior. Transposed to more recently evolved vertebrates such as mammals, we believe that this knowledge will eventually be important to elaborate strategies to restore normal function in patients with motor disorders. The MLR is at present a target for deep brain stimulation to improve locomotor function in Parkinson's disease patients as well as in patients with partial spinal cord injury. It is therefore crucial to understand the intricate mechanisms by which the MLR operates.
It is also essential to understand the inputs to the MLR. We recently described a direct projection from the posterior tuberculum (PT in the figure above) to the MLR. The posterior tuberculum in most interesting because it contains neurons that are homologous to the dopaminergic neurons of the substantia nigra of humans and other mammals. We recently showed that the same dopamine neurons that project to the striatum and are affected in Parkinson's disease also project downward to the MLR and play a role in modulating locomotor movements.
This research is supported by the Canadian Institutes of Health Research.
