Transient axonal pathways develop during the ontogenesis of the central nervous system, but generally retract through maturation such that adult patterns of connectivity are formed. Our recent studies have identified a transient projection from the somatosensory areas of the cerebral cortex to the cerebellum in neonatal kittens. The proposed experiments will examine two hypothetical roles for transient cerebrocerebellar projections. First, cerebro-cerebellar axons may serve to organize and stabilize the termination of other mossy fibers, which are highly organized in the adult, into functionally appropriate areas of the cerebellum. To test this hypothesis small lesions will be made in the hindlimb area of the primary somatosensory cortex in newborn kittens. After the kittens mature the organization of afferent input from brain stem nuclei to hindlimb somatosensory areas of the cerebellum will be mapped by utilizing the retrograde transport of horseradish peroxidase (HRP). The disorganization of neurons projecting to those areas of the cerebellar cortex which did not receive a transient cerebro-cerebellar projection would indicate that cerebro-cerebellar axons serve to validate other cerebellar mossy fiber systems. Secondly, cerebro-cerebellar projections may provide a substrate for functional compensation after lesions early in development that destroy somatosensory input to the cerebellum. Lesions will be made in the neonate in either the middle cerebellar peduncle to interrupt the ponto-cerebellar system relaying somatosensory information from the neocortex, or the inferior cerebellar peduncle to disrupt somatosensory input from brain stem and spinal neurons. Both orthograde (autoradiographic technique) and retrograde (HRP technique) labeling methods will be used to demonstrate any persistance of cerebro-cerebellar axons in juvenile kittens. Their presence would prove that this normally transient pathway can persist after neonatal lesions and possibly could provide an alternative pathway through which the """"""""developmentally injured"""""""" cerebellum could obtain sensory information. The results from these studies will provide much needed and important data concerning the function and plasticity of transient axonal pathways during the normal development of the central nervous system. They also will provide valuable data on the organization of mossy fibers early in development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020227-03
Application #
3400484
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Alisky, J M; Tolbert, D L (1997) Quantitative analysis of converging spinal and cuneate mossy fibre afferent projections to the rat cerebellar anterior lobe. Neuroscience 80:373-88
Tolbert, D L; Gutting, J C (1997) Quantitative analysis of cuneocerebellar projections in rats: differential topography in the anterior and posterior lobes. Neuroscience 80:359-71
Wolf, L W; LaRegina, M C; Tolbert, D L (1996) A behavioral study of the development of hereditary cerebellar ataxia in the shaker rat mutant. Behav Brain Res 75:67-81
Tolbert, D L; Ewald, M; Gutting, J et al. (1995) Spatial and temporal pattern of Purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia. J Comp Neurol 355:490-507
Tolbert, D L; Pittman, T; Alisky, J M et al. (1994) Chronic NMDA receptor blockade or muscimol inhibition of cerebellar cortical neuronal activity alters the development of spinocerebellar afferent topography. Brain Res Dev Brain Res 80:268-74
Alisky, J M; Tolbert, D L (1994) Differential labeling of converging afferent pathways using biotinylated dextran amine and cholera toxin subunit B. J Neurosci Methods 52:143-8
Tolbert, D L; Alisky, J M; Clark, B R (1993) Lower thoracic upper lumbar spinocerebellar projections in rats: a complex topography revealed in computer reconstructions of the unfolded anterior lobe. Neuroscience 55:755-74
La Regina, M C; Yates-Siilata, K; Woods, L et al. (1992) Preliminary characterization of hereditary cerebellar ataxia in rats. Lab Anim Sci 42:19-26
Alisky, J M; Swink, T D; Tolbert, D L (1992) The postnatal spatial and temporal development of corticospinal projections in cats. Exp Brain Res 88:265-76
Tolbert, D L (1989) Absence of impulse activity in cortical neurons with transient projections to the cerebellum. Brain Res Dev Brain Res 50:241-9

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