The remarkable ability of fish and amphibians to regenerative nerve cells and axonal connections is often contrasted with the limited recovery of mammalian species. Those regions of the nervous system that regenerative are those that continue to grow and develop through the life of cold-blooded vertebrates. The relationship between continuing development and regenerative capability makes it imperative to determine whether region of the mammalian nervous system may similar continue to add neurons during postnatal life. Compelling evidence supports the contention that granule cells of the cerebellum, olfactory bulb, and hippocampus continue to proliferate at least through juvenile life in several mammalian species. With this evidence, the possibility of enlisting these persistent developmental mechanisms to restore neurons lost to injury or disease become more salient. Our work in frog shows that neurons may be added by a mechanism other than the birth of new cells. We have shown that late differentiation of committed, but less-differentiated (type-L) neurons add to the existing pool of neurons of neurons in several regions of the nervous system. Recently, we extend our studies to the rat and showed that the number of neurons in sensory ganglia of the lumbar spinal cord is 20-30% greater in 8-0-day rats than in neonates (Popken and Farel, J. Comp. Neurol. 386: 8-15, 1997). This increase is demonstrable using estimates of neuron number based on counts of neuronal profiles or a stereological method, the physical disector.
The aims proposed here will delineate whether the sensory neurons in rat are added by mitosis or late differentiation of committed precursors; whether sensory neurons are added throughout life or only during stages of rapid body growth; and whether neuron addition is associated with increased axonal projections to the periphery. We will also determine whether the presumed population of type-L neurons differs from nature sensory neurons in the functional differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037524-02
Application #
6151614
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Heetderks, William J
Project Start
1999-05-01
Project End
2003-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
2
Fiscal Year
2000
Total Cost
$193,569
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Farel, Paul B (2003) Late differentiation contributes to the apparent increase in sensory neuron number in juvenile rat. Brain Res Dev Brain Res 144:91-8
Farel, Paul B (2002) Sensory neuron addition in juvenile rat: time course and specificity. J Comp Neurol 449:158-65
Berg, J S; Farel, P B (2000) Developmental regulation of sensory neuron number and limb innervation in the mouse. Brain Res Dev Brain Res 125:21-30
Farel, P B; McIlwain, D L (2000) Neuron addition and enlargement in juvenile and adult animals. Brain Res Bull 53:537-46