The goal of this research is to elucidate the neural mechanisms in the spinal cord that underlie the generation of rhythmic locomotory output and to determine, at the cellular level, the role of putative amino acid transmitters in the production and control of spinal locomotion. The studies are being done on an in vitro lamprey spinal cord preparation that generates """"""""fictive locomotion"""""""", the neuronal correlated of locomotory behavior. The first objective of the study is to identify the spinal neurons involved in pattern generation. The locomotory networks must produce both alternating rhythmic output and appropriate patterns for intersegmental coordination. We hypothesize that the rhythmicity is produced by inherent properties of individual neurons of the network timed by synaptic drive and that intersegmental coordination is the result of the existence of relatively local oscillators in combination with the characteristics of ascending and descending coupling along the length of the spinal cord. Experiments will be done to test these hypotheses using a combination of intracellular, lesion and pharmacological techniques. The test require a quantitative description of the magnitude, phase relationships and segmental distribution of the synaptic inputs from propriospinal neurons to motoneurons and between propriospinal neurons. Amino acid transmitter receptor agonists and antagonists have powerful effects on the locomotory motor output generated by the spinal cord. The second objective of the research is to determine the role of amino acid transmitters in pattern generation by studying the effects of these transmitter receptor agonists and antagonists on the activity of individual interneurons during fictive locomotion. The results of this study will provide insights into how the spinal a network is organized and at what level in the organization of the network thee agents operate. Furthermore, any agents found to act specifically to turn on or modulate spinal centers for locomotion amy be related to transmitters that function in the control of locomotion by descending systems from the brain, control that is lost following spinal transection.
