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Séminaire - Réjean DubucThe multifunctional mesencephalic locomotor region: possible links with Parkinson’s disease

Abstract :

Locomotion is a basic motor act that requires the coordinated activation of a large number of muscles throughout the body. The basic muscle synergies are generated by populations of spinal cord neurons collectively referred to as central pattern generators (CPGs). Supraspinal neurons play a crucial role in activating the spinal CPGs for locomotion. One key supraspinal area is the mesencephalic locomotor region (MLR), first discovered in the 1960s by a group of Russian neuroscientists. 

The MLR was found to control the locomotor output in a graded fashion, not unlike a rheostat. In addition, it was shown that its control onto the spinal cord networks was exerted via the brainstem reticulospinal cells. With my research group in Montreal, we have extended on these results using the lamprey model to examine the detailed connectivity of the MLR with reticulospinal cells and other populations of brainstem neurons.

This presentation will focus on the downstream projections from the MLR to different populations of reticulospinal cells. It will also describe how the MLR acts via an additional parallel pathway to activate muscarinoceptive cells that boost the locomotor output. We have recently shown that the MLR also projects to the brainstem respiratory generating area and that this projection plays a key role in adjusting the respiratory drive to the locomotor output. Our results stress the importance of a neural feed-forward system adjusting respiration to the increased oxygen demand occurring during movement. We are presently examining some of the inputs to the MLR and this will also be addressed in the presentation.

We have uncovered a direct dopaminergic projection from the lamprey homologous of the A9/A10 dopaminergic cell groups to the MLR. This projection controls locomotion and we believe that its presence may have considerable implications in understanding the neural changes that occur in Parkinson’s disease.

Selected publications

  • Smetana R, Juvin L, Dubuc R, Alford S.  A parallel cholinergic brainstem pathway for enhancing locomotor drive.  Nature Neuroscience, 13: 731-738, 2010.
  • Derjean D, Moussaddy A, Atallah E,St-Pierre M, Auclair F, Chang S, Ren X, Zielinski B, Dubuc R.  A novel neural substrate for the transformation of olfactory inputs into motor output.  PLos Biology,8: e1000567, 2010.
  • Antri M, Fénelon K, Dubuc R.  The contribution of synaptic inputs to sustained depolarizations in reticulospinal neurons.  J. Neurosci.,29: 1140-1151, 2009.
  • Gravel J, Brocard F, Gariépy JF, Lund JP, Dubuc R.  Modulation of respiratory activity by locomotion in lampreys.  Neuroscience, 144: 1120-1132, 2007.
  • Brocard F, Dubuc R.  Differential contribution of RS cells to the control of locomotion induced by the mesencephalic locomotor region.  J. Neurophysiol., 90: 1714-1727, 2003.
  • Viana Di Prisco G, Pearlstein E, Robitaille R, Dubuc R.  Role of sensory-evoked NMDA plateau potentials in the initiation of locomotion.  Science, 278: 1122-1125, 1997.

Sandrine Bertrand