The goal of the proposed 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 study will be done on an in vitro lamprey spinal cord preparation that generates """"""""fictive locomotion"""""""", the neuronal correlate of locomotory behavior. The first objective of the proposed study is to identify and describe the interneurons or types of interneurons that may be a part of the locomotory central pattern generator, those neurons with membrane potential oscillations and/or spike activity correlated with the pattern of efferent discharge. The description of each neuron will include physiological properties and morphological characteristics, as revealed by intracellular dye injection. Evidence of synaptic connections between the neuron being characterized and other components of the spinal cord will be gathered and tests to determine the role each neuron plays in the network will be performed. 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 proposed research is to determine the effects of amino acid neurotransmitter receptor agonists and antagonists on the central pattern generator by combining a study of the effects of these pharmacological agents on the activity of individual interneurons during fictive locomotion with a detailed description of each recorded neuron's physiological and morphological characteristics. The results of this study can provide insights into how the spinal network is organized and at what level in the organization of the network these agents operate. Furthermore, any agents found to act specifically to turn on or modulate spinal centers for locomotion may be related to transmitter than 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 #
5R01NS022360-03
Application #
3404617
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
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
Miller, W L; Sigvardt, K A (2000) Extent and role of multisegmental coupling in the Lamprey spinal locomotor pattern generator. J Neurophysiol 83:465-76
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