The nervous system must cope with increasing body size as the juvenile matures to a full-grown adult. Without some form of compensation, sensory discrimination and motor precision would be degraded as the ratio of neurons to target size decreased. One solution to this problem is to add neurons. Using the bullfrog as an experimental model, the first objective is directed toward this fundamental question of neural organization: Are neurons added to the nervous system during adulthood? Our initial studies provide strong preliminary evidence that neurons are indeed added as a function of body size to both the central and peripheral nervous systems. Further aims for this objective include determining the mechanism whereby neurons are added and the relationship between neuron number and target size. The proposed experiments entail cell counts in frogs of different sizes, the use of antibodies directed against cellular markers characteristic of neurons of a particular type, and injection of 3H-thymidine to determine whether new neurons are being born during adulthood. To be of use, neurons that are added must innervate their proper targets, which in turn implies that mechanisms of axon guidance are still operating in the established nervous system. However, many neurons, such as spinal motoneurons in the bullfrog tadpole, are able to regenerate axons to their proper targets only if axotomy occurs early in development (Farel and Bemelmans, 1986; Farel and Wray, 1989). The second objective is directed toward understanding mechanisms of axon guidance during regeneration and the reasons for their failure to be expressed after early developmental stages. Attaining this objective is a first step toward understanding how axons of neurons that are added during adulthood are able to innervate their appropriate targets. These experiments entail assessing regenerative specificity by the use of retrogradely transported markers, explant cultures to test for diffusible tropic factors, and electron microscopy to monitor hindlimb development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS016030-10A2
Application #
3396624
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1980-05-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Popken, G J; Farel, P B (1997) Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods. J Comp Neurol 386:8-15
Meeker, M L; Farel, P B (1997) Neuron addition during growth of the postmetamorphic bullfrog: sensory neuron and axon number. J Comp Neurol 389:569-76
Popken, G J; Farel, P B (1996) Reliability and validity of the physical disector method for estimating neuron number. J Neurobiol 31:166-74
St Wecker, P G; Baek, J K; Farel, P B (1995) Principal neurons of the lumbar sympathetic ganglia increase in number with body size. J Comp Neurol 357:117-23
St Wecker, P G; Farel, P B (1994) Hindlimb sensory neuron number increases with body size. J Comp Neurol 342:430-8
Meeker, M L; Farel, P B (1993) Coincidence of Schwann cell-derived basal lamina development and loss of regenerative specificity of spinal motoneurons. J Comp Neurol 329:257-68
Farel, P B; Wray, S E; Meeker, M L (1993) Size-related increase in motoneuron number: evidence for late differentiation. Brain Res Dev Brain Res 71:169-79
Farel, P B; Meeker, M L (1993) Developmental regulation of regenerative specificity in the bullfrog. Brain Res Bull 30:483-90
Farel, P B; St Wecker, P G; Wray, S E (1992) Neuron addition in the postmetamorphic frog. Exp Gerontol 27:111-24
Farel, P B; Wray, S E (1992) Neuromuscular specificity following cross-stage hindlimb transplantation. Exp Neurol 116:180-8

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