Impairment of walking is a debilitating consequence of spinal cord injury resulting from the disruption of neuronal pathways projecting from the brain to the spinal cord neurons which generate locomotion. Fortunately, after injury, these spinal neurons retain the neurotransmitter receptors used by descending pathways originating in the brain to control them. This leaves open the possibility that a therapeutic improvement in the ability to walk can be achieved, providing that the appropriate neurotransmitter is made available to activate or modulate the activity of these neurons. This forms the basis of a “neurotransmitter enhancement therapy” following spinal cord injury. The long-term goal of my research is to develop and optimize treatments for spinal cord injury based on neurotransmitter enhancement strategies.
For spinal cords which are relatively large such as in the human, applications of transmitters to the surface of the spinal cord are likely more beneficial for long-term continuous modulation of neuronal activity of neurons located in superficial areas of the spinal cord and may be better suited for targeting sensory-related functions of sensory and motor systems. For directly affecting locomotor generating neurons and their circuits located in deeper parts of the spinal cord, very high concentrations of transmitters would be needed, increasing the risk of unwanted side-effects. As an alternative strategy, we are exploring the use of deep brain stimulation to enhance transmitter release from surviving pathways innervating deeper target (locomotor) areas of the spinal cord following incomplete spinal cord injury. An advantage of the use of deep brain stimulation is that it is adjustable and would allow one to increase transmitter release as needed, duplicating the temporal patterns of release observed in the uninjured spinal cord during walking.

• Locomotor-activated neurons of the cat. II. Noradrenergic innervation and colocalization with NEa 1a or NEa 2b receptors in the thoraco-lumbar spinal cord.
• Locomotor-activated neurons of the cat. I. Serotonergic innervation and co-localization of 5-HT7, 5-HT2A, and 5-HT1A receptors in the thoraco-lumbar spinal cord.
• Mechanism for activation of locomotor centers in the spinal cord by stimulation of the mesencephalic locomotor region.

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