Electrical stimulation of the mesencephalic locomotor region (MLR) is known to initiate and maintain walking in the brainstem- transected animal by modulating locomotion oscillators present in the spinal cored. Over the past several years we have described many of the anatomical and functional characteristics of the MLR. The goal of this proposal is to gain a better understanding of the function and electrical/neurochemical control of additional locomotion- and posture-inducing sites at each of three levels of the adult rat neuraxis - medulla, cervical enlargement, and lumbosacral enlargement. This represents a logical progression form the MLR, which projects to the ventromedial reticular formation (MED), to the MED which, in turn, projects to the spinal cord and, then, to the spinal cord itself. The proposal is divided into two series of experiments - the first with intact spinal cords and the second with transected spinal cords. In the first series, the proposed research will extend our finding of electrically induced locomotion following stimulation of the MED to chemical activation of this site. We will further characterize the MED transmitter system by identifying neuroactive agents which facilitate or inhibit MLR induced locomotion. Electrical stimulation and chemical injections will be used to characterize locomotor control systems in the spinal enlargements and in pre- enlargement regions. In the second series, electrical and chemical activation of locomotion- and posture-inducing systems will be examined in transected (at T10 spinal cords. The first experiment utilizes acutely spinalized animals and the second chronically transected animals. Taken together, these studies will provide information on the control of spinal locomotion oscillators in "intact" spinal cords and the changes in that control following acute and chronic "denervation". The overall goal of these experiments is to electrically and neurochemically control posture and locomotion and to provide a basis for the design of appropriate electro/chemotherapeutic strategies in cases of spinal cord injury.

R01NS021981

1985-04-01

1993-03-31