Target-selection and the elaboration of terminal arbors are two of the most critical tasks undertaken by growing axons. Yet a significant hiatus remains in our understanding of how cells in the vertebrate nervous system perform these operations. The proposed experiments are designed to advance our knowledge of the structural basis for the formation of precise connections, an to use this knowledge to analyse the nature of axonal growth in mature brains, growth obtained by challenging the adult brain with an environment which is novel, yet permissive for growth. The barrel field cortex of the rat provides a compelling model for addressing these issues. The homeomorphic relationships between the barrel field neurons, thalamic afferent arbors, and the array of mystical vibrissae on the snout will be exploited to examine morphogenetic events underlying afferent-target interactions which lead to the normal development and plasticity of sensory maps in the neocortex. Anatomical and immunohistochemical techniques along with compute-aided microscopy will reveal strategies employed by axons in reaching and arborizing within normal and novel targets. Progressive changes in axon arbor morphologies will be correlated with expression of major growth-activity, and with the clustering of synaptic terminals . Similar studies will be conducted in animals with i) early alterations of the sensory periphery, thus changing the pattern of input to thalamocortical projection cells and ii) alterations in the target tissue itself, to probe target-derived influences on projection patterns. This combination of experiments will elucidate ways in which the growth state of young axons can be recapitulated in mature brains, an issue of critical importance for repair of damage in the human nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027678-03
Application #
3414047
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Other Domestic Higher Education
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Vercelli, A; Repici, M; Biasiol, S et al. (1999) Maturation of NADPH-d activity in the rat's barrel-field cortex and its relationship to cytochrome oxidase activity. Exp Neurol 156:294-315
Sendemir, E; Erzurumlu, R S; Jhaveri, S (1996) Differential expression of acetylcholinesterase in the developing barrel cortex of three rodent species. Cereb Cortex 6:377-87
Erzurumlu, R S; Jhaveri, S (1995) Target influences on the morphology of trigeminal axons. Exp Neurol 135:1-16
Li, Y; Erzurumlu, R S; Chen, C et al. (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76:427-37
Erzurumlu, R S; McKay, R D; Jhaveri, S (1994) Morphological specification of trigeminal neurites depends on target fields. Brain Res Dev Brain Res 83:132-7
Erzurumlu, R S; Jhaveri, S; Takahashi, H et al. (1993) Target-derived influences on axon growth modes in cultures of trigeminal neurons. Proc Natl Acad Sci U S A 90:7235-9
Erzurumlu, R S; Jhaveri, S (1992) Trigeminal ganglion cell processes are spatially ordered prior to the differentiation of the vibrissa pad. J Neurosci 12:3946-55
Erzurumlu, R S; Jhaveri, S (1992) Emergence of connectivity in the embryonic rat parietal cortex. Cereb Cortex 2:336-52
Jhaveri, S; Erzurumlu, R S; Crossin, K (1991) Barrel construction in rodent neocortex: role of thalamic afferents versus extracellular matrix molecules. Proc Natl Acad Sci U S A 88:4489-93
Blue, M E; Erzurumlu, R S; Jhaveri, S (1991) A comparison of pattern formation by thalamocortical and serotonergic afferents in the rat barrel field cortex. Cereb Cortex 1:380-9