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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022360-05
Application #
3404618
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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Miller, W L; Sigvardt, K A (1998) Spectral analysis of oscillatory neural circuits. J Neurosci Methods 80:113-28
Sigvardt, K A; Williams, T L (1996) Effects of local oscillator frequency on intersegmental coordination in the lamprey locomotor CPG: theory and experiment. J Neurophysiol 76:4094-103
Williams, T L; Sigvardt, K A (1994) Intersegmental phase lags in the lamprey spinal cord: experimental confirmation of the existence of a boundary region. J Comput Neurosci 1:61-7
Williams, T L; Sigvardt, K A; Kopell, N et al. (1990) Forcing of coupled nonlinear oscillators: studies of intersegmental coordination in the lamprey locomotor central pattern generator. J Neurophysiol 64:862-71
Alford, S; Sigvardt, K A; Williams, T L (1990) GABAergic control of rhythmic activity in the presence of strychnine in the lamprey spinal cord. Brain Res 506:303-6
Alford, S; Williams, T L; Sigvardt, K A (1990) Effects of bicuculline and strychnine on synaptic inputs to edge cells during fictive locomotion. Brain Res 509:137-40
Alford, S; Sigvardt, K A (1989) Excitatory neurotransmission activates voltage-dependent properties in neurons in spinal motor system of lamprey. J Neurophysiol 62:334-41
McClellan, A D; Sigvardt, K A (1988) Features of entrainment of spinal pattern generators for locomotor activity in the lamprey spinal cord. J Neurosci 8:133-45