This Program Project is directed at understanding mechanisms of development of the cerebral cortex. Particular attention is focused on understanding the process of ingrowth of thalamocortical afferents and the role that these developing afferents play in the differentiation of cortex. Five individual projects bring a variety of complementary modern experimental approaches to address these issues of cortical development, using sensory cortex of rodents as a model system. Studies involve the use of: 1) axonal tracing techniques with light, electron and laser confocal microscopy to study morphological development of thalamocortical afferents [Projects 1, 2, 3]; 2) whole cell current and voltage clamping, and histochemical measures of metabolic activity to study physiological development of thalamocortical systems [Projects 2 and 3]; 3) intracellular dye injections, in situ hybridization, immunocytochemistry, and electron microscopy to study morphological development of cortical neurons [Projects 1, 2, 3, 4 and 5]; and 4) receptor binding assays, in situ hybridization, immunocytochemistry and whole cell clamping to study functional development of cortical neurons [Projects 2, 3, 4 and 5]. The use of laser confocal microscopy in a core facility will allow the relationships between developing afferent axons and differentiating cortical neurons to be studied in detail. this program is designed to maximize the complementary nature of these studies so that results from morphological, physiological, pharmacological, and molecular biological studies can be integrated to provide a comprehensive understanding of the mechanisms of development of the cerebral cortex. Such an understanding of fundamental mechanisms regulating development of the cerebral cortex is vital for determining the causes of developmental neurological disorders affecting the human cerebral cortex, and for planning strategies for therapeutic and preventative interventions.