Motoneuron differentiation and the formation of specific synaptic contacts arise from interactions between expression of genetic information, and epigenetic influences that are extrinsic to the neuron. The objectives of this proposal are to investigate and determine the mechanisms underlying neuronal differentiation and synaptogenesis in mammalian spinal cords. Studies are focused on the mechanisms by which newly formed central and peripheral synapses regulate the developmental changes in motoneuron electrical and pharmacological properties. Development-related increases in motoneuron excitability and in the efficacy of synaptic transmission will be studied using electrophysiological recording techniques. The importance of intracellular Ca2+ in increasing the efficacy of developing sensory-motor synapses will be determined by relating the developmental changes in spontaneous and pharmacologically induced changes in intracellular Ca2+ to physiological changes in synaptic transmission. Three preparations will be used: (l) isolated lumbar spinal cords with attached muscle nerves, (2) spinal cord slices in which sensory-motor pathways are preserved and neurons can be visualized for electrophysiological recordings and Ca2+ imaging, and (3) spinal cord explants in which motoneurons and synaptic pathways differentiate in the controlled environment of organ culture. Our recent studies established the pattern and time course of motoneuron development and synapse formation in utero, and will guide our studies on motoneuron development in organ culture. The proposed experiments are designed to increase our understanding of the roles of extracellular factors in synaptogenesis and neuronal differentiation. This knowledge will provide insight into mechanisms underlying long-term synaptic interactions between neurons in the central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023808-12
Application #
2655445
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Spinella, Giovanna M
Project Start
1986-07-01
Project End
2000-01-31
Budget Start
1998-02-01
Budget End
2000-01-31
Support Year
12
Fiscal Year
1998
Total Cost
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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