The hamster pyramidal tract arising from the sensorimotor cortex innervates all segments of the spinal cord, and develops entirely postnatally. When axons in the medullary pyramid are severed early in development, pyramidal tract axons regrow, establish appropriate synapses in the cervical spinal cord and thus preserve fine motor control of the forelimb. In order to compare normal development of a CNS pathway with CNS axons regenerating after injury, the developing and regenerating hamster pyramidal tract will be studied with respect to neuronal topography, axon guidance, growth associated proteins, morphology of axon arborizations, and development of motor behavior. Development of topography in corticospinal neurons will be mapped by retrograde double labeling with fluorescent dyes. Growing pyramidal tract axons in the decussation will be labeled with HRP and their relationship to non-neuronal processes in the cellular environment examined with light and electron microscopy. During development, putative glial guides at the decussation will be characterized ultrastructurally and with immunocytochemical localization of cell-specific antisera to cytoskeletal elements to establish their glial identity and to follow changes in their filament proteins as pyramidal fibers grow into the region. Rapidly transported membrane proteins, designated growth associated proteins (GAPs), will be analyzed with gel electrophoresis to determine whether GAPs represent a discrete set of proteins whose expression is characteristic of neurons during axonal outgrowth in the developing and regenerating CNS. Branching patterns characteristic of developing, mature and regenerating axon arbors will be described morphologically by labeling axons with HRP in vitro slice preparations. The emergence of specific behaviors requiring sensorimotor integration will be correlated with development of corticospinal axons. Filmed behavior of hamsters with infant lesions of the pyramidal tract will be analyzed to measure the ability or regenerating axons to preserve the normal development of speed, strength and accuracy of specific motor behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS014428-13
Application #
3395546
Study Section
Biopsychology Study Section (BPO)
Project Start
1978-04-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
13
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Biswas, Sayantanee; Kalil, Katherine (2018) The Microtubule-Associated Protein Tau Mediates the Organization of Microtubules and Their Dynamic Exploration of Actin-Rich Lamellipodia and Filopodia of Cortical Growth Cones. J Neurosci 38:291-307
Kalil, Katherine; Dent, Erik W (2014) Branch management: mechanisms of axon branching in the developing vertebrate CNS. Nat Rev Neurosci 15:7-18
Li, Li; Fothergill, Thomas; Hutchins, B Ian et al. (2014) Wnt5a evokes cortical axon outgrowth and repulsive guidance by tau mediated reorganization of dynamic microtubules. Dev Neurobiol 74:797-817
Hutchins, B Ian; Li, Li; Kalil, Katherine (2012) Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum. Sci Signal 5:pt1
Kalil, Katherine; Li, Li; Hutchins, B Ian (2011) Signaling mechanisms in cortical axon growth, guidance, and branching. Front Neuroanat 5:62
Hutchins, B Ian; Li, Li; Kalil, Katherine (2011) Wnt/calcium signaling mediates axon growth and guidance in the developing corpus callosum. Dev Neurobiol 71:269-83
Li, Li; Hutchins, B Ian; Kalil, Katherine (2010) Wnt5a induces simultaneous cortical axon outgrowth and repulsive turning through distinct signaling mechanisms. Sci Signal 3:pt2
Li, Li; Hutchins, B Ian; Kalil, Katherine (2009) Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms. J Neurosci 29:5873-83
Hutchins, B Ian; Kalil, Katherine (2008) Differential outgrowth of axons and their branches is regulated by localized calcium transients. J Neurosci 28:143-53
Kalil, Katherine; Dent, Erik W (2005) Touch and go: guidance cues signal to the growth cone cytoskeleton. Curr Opin Neurobiol 15:521-6

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