Spinal networks that produce locomotor-like rhythmic electrical activity are formed at early stages of neuronal differentiation in the rat spinal cord. Previous studies have suggested that each side of the spinal cord contains a group of spinal interneurons that form a network referred to as the central pattern generator, which produces rhythmic electrical activity independently of supraspinal and peripheral sensory inputs. The coordinated oscillatory potentials in opposite sides of the spinal cord are thought to be responsible for the left/right alternating hind limb movements. The primary goal of this application is to determine the developmental changes in the organization and functional integration of distinct neural networks that trigger rhythmic electrical activity and coordinate bilateral activity in the developing mammalian spinal cord. Real-time images of voltage-sensitive fluorescent dye will be used to record changes in electrical activity in various areas of the isolated spinal cord. The main objectives of our application are: (1) To characterize the changes in the spatiotemporal pattern of spontaneous coordinated rhythmic oscillations during embryonic and postnatal development, and study the properties of the potential underlying those activities. (2) To investigate the spatial organization and functional integration of rhythm-generating networks and networks that coordinate the oscillatory electrical activity between the ipsilateral and contralateral sides of the spinal cord. Mechanical lesions at specific sites and local pharmacological block of synaptic transmission will be used to test the role of specific pathways in the generation of locomotor-like activity. (3) To determine the functional relationship between neural pathways that mediate spontaneous and pharmacologically induced rhythmic oscillations at the onset of coordinated bilateral activity. Experiments will be carried out using complementary biophysical and electrophysiological approaches in thick spinal cord slices in which neural networks are preserved. These studies will increase our understanding of the mechanisms underlying the establishment of rhythm-generating networks and the complex functional integration of rhythmic activity that results in bilateral coordinated activity. The findings will be valuable for gaining insight into factors that might regulate long-term cellular interactions and synaptic plasticity in mature neural networks.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023808-16
Application #
6639396
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Leblanc, Gabrielle G
Project Start
1986-07-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
16
Fiscal Year
2003
Total Cost
$228,576
Indirect Cost
Name
University of Wisconsin Madison
Department
Physiology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Ziskind-Conhaim, Lea; Hochman, Shawn (2017) Diversity of molecularly defined spinal interneurons engaged in mammalian locomotor pattern generation. J Neurophysiol 118:2956-2974
Mavlyutov, T A; Epstein, M L; Liu, P et al. (2012) Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N,N'-dimethyltryptamine forming enzyme, indole-N-methyl transferase. Neuroscience 206:60-8
Wu, Linying; Sonner, Patrick M; Titus, David J et al. (2011) Properties of a distinct subpopulation of GABAergic commissural interneurons that are part of the locomotor circuitry in the neonatal spinal cord. J Neurosci 31:4821-33
Ziskind-Conhaim, Lea; Mentis, George Z; Wiesner, Eric P et al. (2010) Synaptic integration of rhythmogenic neurons in the locomotor circuitry: the case of Hb9 interneurons. Ann N Y Acad Sci 1198:72-84
Hinckley, Christopher A; Wiesner, Eric P; Mentis, George Z et al. (2010) Sensory modulation of locomotor-like membrane oscillations in Hb9-expressing interneurons. J Neurophysiol 103:3407-23
Mavlyutov, T A; Epstein, M L; Andersen, K A et al. (2010) The sigma-1 receptor is enriched in postsynaptic sites of C-terminals in mouse motoneurons. An anatomical and behavioral study. Neuroscience 167:247-55
Ziskind-Conhaim, Lea; Wu, Linying; Wiesner, Eric P (2008) Persistent sodium current contributes to induced voltage oscillations in locomotor-related hb9 interneurons in the mouse spinal cord. J Neurophysiol 100:2254-64
Hinckley, Christopher A; Ziskind-Conhaim, Lea (2006) Electrical coupling between locomotor-related excitatory interneurons in the mammalian spinal cord. J Neurosci 26:8477-83
Hinckley, C; Seebach, B; Ziskind-Conhaim, L (2005) Distinct roles of glycinergic and GABAergic inhibition in coordinating locomotor-like rhythms in the neonatal mouse spinal cord. Neuroscience 131:745-58
Ziskind-Conhaim, Lea; Redman, Stephen (2005) Spatiotemporal patterns of dorsal root-evoked network activity in the neonatal rat spinal cord: optical and intracellular recordings. J Neurophysiol 94:1952-61

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