A functional cerebral cortex is essential for virtually all higher order behavioral processes including sensorimotor integration, cognition, use of language and reasoning. The quintessential feature of cerebral cortex is its highly laminated structure with cascades of serial feed-forward and feed-back innervation. The development of the mammalian neocortex is characterized by a number of distinctive (but highly interactive) cellular processes in neurons and glia. Epigenetic factors that interfere with any of these processes in the fetus and/or neonate (such as hypoxia, exposure to infectious agents, environmental toxins, alcohol/drug exposure, nutritional deficits or an impoverished sensory/cognitive environment) are likely to result in a functionally compromised cerebral cortex, often with profound consequences for cognitive development. The overall goal of this project is to define the mechanisms that mediate certain key events in the normal development of the cerebral cortex. In particular, the major excitatory (those that use glutamate as a neurotransmitter) neuronal pathways in the cerebral cortex will be studied with respect to neuronal synaptogenesis, differentiation of the myelin-producing oligodendrocytes and the regulation of neuronal glutamate release. A relatively newly discovered gaseous molecule -- nitric oxide (NO) -- has been suggested to play a major role in the development, refinement and regulation of synaptic architecture and synaptic efficacy in the central nervous system (CNS), including the cerebral cortex. The proposed experiments will address the role of this molecule in the development and refinement of cortical glutamatergic synapses, the differentiation of functional oligodendrocytes, and the regulation of the release of glutamate - the major excitatory neurotransmitter that also can act as an excitotoxin, during postnatal development of the cerebral cortex.
The aims of the project are to evaluate the role of nitric oxide in i) the development of synapse formation, ii) myelinogenesis and iii) glutamate release, respectively. The first part will evaluate the morphological development of NO generating circuitry in the cortex and the ability of NO to influence cortical neuron neurite outgrowth and synaptogenesis. The second part will evaluate the role of NO in the differentiation of immature oligodendrocytes into functional myelin forming cells. The third part will evaluate the development of NO signaling in the cortex and its ability to modulate glutamate release.

Project Start
1998-08-01
Project End
2000-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Dresbach, Thomas; Torres, Viviana; Wittenmayer, Nina et al. (2006) Assembly of active zone precursor vesicles: obligatory trafficking of presynaptic cytomatrix proteins Bassoon and Piccolo via a trans-Golgi compartment. J Biol Chem 281:6038-47
Tamura, Tsunenobu; Goldenberg, Robert L; Chapman, Victoria R et al. (2005) Folate status of mothers during pregnancy and mental and psychomotor development of their children at five years of age. Pediatrics 116:703-8
Fenster, Steven D; Kessels, Michael M; Qualmann, Britta et al. (2003) Interactions between Piccolo and the actin/dynamin-binding protein Abp1 link vesicle endocytosis to presynaptic active zones. J Biol Chem 278:20268-77
Shapira, Mika; Zhai, R Grace; Dresbach, Thomas et al. (2003) Unitary assembly of presynaptic active zones from Piccolo-Bassoon transport vesicles. Neuron 38:237-52
Tamura, Tsunenobu; Goldenberg, Robert L; Ramey, Sharon L et al. (2003) Effect of zinc supplementation of pregnant women on the mental and psychomotor development of their children at 5 y of age. Am J Clin Nutr 77:1512-6
Altrock, Wilko D; tom Dieck, Susanne; Sokolov, Maxim et al. (2003) Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon. Neuron 37:787-800
Dick, Oliver; tom Dieck, Susanne; Altrock, Wilko Detlef et al. (2003) The presynaptic active zone protein bassoon is essential for photoreceptor ribbon synapse formation in the retina. Neuron 37:775-86
Tamura, Tsunenobu; Goldenberg, Robert L; Hou, Jinrong et al. (2002) Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 140:165-70
Fenster, Steven D; Garner, Craig C (2002) Gene structure and genetic localization of the PCLO gene encoding the presynaptic active zone protein Piccolo. Int J Dev Neurosci 20:161-71
Wu, Hongju; Nash, Joanne E; Zamorano, Pedro et al. (2002) Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking. J Biol Chem 277:30928-34

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