Maps of body surfaces are central to brain development and function. Yet the processes by which these maps form in cerebral cortex are very poorly understood. Understanding the mechanisms underlying cortical map development is the long-range goal of this research.
Specific aims of this proposal are to: Determine if map dimensions are influenced by whisker activation in GAP-43 (+/-) barrel cortex. Determine if barrel dimensions are correlated with GAP-43 expression in (+/-) mice. Determine if barrel dimensions in GAP-43 (+/-) mice are NMDA receptor dependent. Determine if barrel maturation is delayed by reduced GAP-43 expression. We propose to answer these questions using as a model system a mouse line with reduced or no expression of Growth-Associated Protein (GAP-43 (+/-) and (-/-)). The power of our approach is demonstrated by our recent discovery of disrupted whisker/barrel maps in GAP-43 (-/-) cortex, and of enlarged barrels and activity-dependent barrel dimensions in GAP-43 (+/-) mice. The mature central nervous system is an extraordinarily complex arrangement of contacts between specialized cells. The precision of the array is necessary for function. Thus, the mechanisms of target selection and formation of stable connections are extremely important in developmental neurobiology. They are critical to understanding congenital abnormalities and dysplasias, and also in potential therapies to restore function after damage to the nervous system [1]. Our discovery of enlarged barrels and activity-dependent barrel dimensions in GAP- 43 (+/-) cortex creates a unique opportunity to dissect the processes of barrel formation. These studies can have a fundamental impact on our understanding of map development in cerebral cortex.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040779-04
Application #
6774748
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Tagle, Danilo A
Project Start
2001-08-15
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$304,000
Indirect Cost
Name
Upstate Medical University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Zaccaria, Kimberly J; McCasland, James S (2012) Emergence of layer IV barrel cytoarchitecture is delayed in somatosensory cortex of GAP-43 deficient mice following delayed development of dendritic asymmetry. Somatosens Mot Res 29:77-88
Zaccaria, K J; Lagace, D C; Eisch, A J et al. (2010) Resistance to change and vulnerability to stress: autistic-like features of GAP43-deficient mice. Genes Brain Behav 9:985-96
Kelly, Emily A; Tremblay, Marie-Eve; McCasland, James S et al. (2010) Postsynaptic deregulation in GAP-43 heterozygous mouse barrel cortex. Cereb Cortex 20:1696-707
Donovan, Stacy L; McCasland, James S (2008) GAP-43 is critical for normal targeting of thalamocortical and corticothalamic, but not trigeminothalamic axons in the whisker barrel system. Somatosens Mot Res 25:33-47
McIlvain, Vera; McCasland, James S (2006) GAP-43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP-43. Anat Rec A Discov Mol Cell Evol Biol 288:143-57
Dubroff, J G; Stevens, R T; Hitt, J et al. (2006) Anomalous functional organization of barrel cortex in GAP-43 deficient mice. Neuroimage 29:1040-8
Dubroff, J G; Stevens, R T; Hitt, J et al. (2005) Use-dependent plasticity in barrel cortex: intrinsic signal imaging reveals functional expansion of spared whisker representation into adjacent deprived columns. Somatosens Mot Res 22:25-35
McIlvain, Vera A; Robertson, Douglas R; Maimone, Margaret M et al. (2003) Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels in neonatal GAP-43 heterozygous mice. J Comp Neurol 462:252-64
Maier, Donna L; Grieb, Ginny M; Stelzner, Dennis J et al. (2003) Large-scale plasticity in barrel cortex following repeated whisker trimming in young adult hamsters. Exp Neurol 184:737-45
Donovan, Stacy L; Mamounas, Laura A; Andrews, Anne M et al. (2002) GAP-43 is critical for normal development of the serotonergic innervation in forebrain. J Neurosci 22:3543-52