Transient axonal projections develop during the normal ontogenesis of pathways in the central nervous system. We have identified a transient projection from lamina V neurons in the primary sensorimotor cortex to the cerebellar cortex and nuclei in neonatal kittens. Neurons in face, forelimb, and hindlimb areas of the primary somatosensory cortex (S-I) project to somatotopically homologous areas of the cerebellar cortex. Many cerebrocerebellar projections are transient collaterals of corticobulbar and corticospinal axons which persist. After reaching their maximum density in the cerebellum in the second postnatal week, all cerebrocerebellar projections are normally eliminated. The regressions of some transient pathways has been shown to be influenced by impulse activity, and there are findings that pathways which are functionally silent are eliminated. We propose two sets of experiments to determine if transient cerebrocerebellar projections are eliminated as the result of: (1) the cell bodies not being respoonsive to orthodromic activation or spontaneously active, (2) cerebrocerebellar axons not propagating action potentials, (3) cerebrocerebellar projections not forming functional synaptic contacts with cerebellar neurons. In the first set of experiments, we will use extracellular unitary recordings to determine the physiological characteristics of cerebrocerebellar projection neurons in S-I. In the second set of experiments, we will determine electrophysiologically if cerebrocerebellar axons propagate action potentials and if stimulation of the cerebral cortex functionally activates cerebellar neurons. In other experiments, we will use EM autoradiographic techniques to determine if cerebrocerebellar axons, orthogradely labeled from tritiated amino acid injection sites in the cerebrum, form synaptic contact with cerebellar neurons. The elimination of transient cerebrocerebellar projections is not predetermined and many will persist after other cerebellar afferents are directly damaged. In a third set of experiments, we will determine if cerebrocerebellar axons persist after lesions which indirectly deafferent the paramedian lobule of face somatosensory input. We anticipate that only projections from the face area of S-I will persist after trigeminal primary afferents are cut, indicating that the stabilization of these projections provides an alternate circuit for functionally relevant information to reach the cerebellum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS020227-04
Application #
3400480
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1989-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
4
Fiscal Year
1987
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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