The normal formation of the cerebral cortex is a prerequisite for attaining higher cognitive, motor and sensory function. This study will examine some basic issues of cortical development: intrinsic and extrinsic factors regulating either differentiation of neurons or connectivity allowing the development of functionally distinct areas of cerebral cortex in mammals. In particular, this proposal will be focusing on the development of one part of the limbic system, the perirhinal cortex. In recent transplantation studies, results have shown there is an early specification of neurons to express a limbic molecular phenotype, the limbic-system-associated membrane protein, LAMP (Barbe and Levitt, 1991; Appendix I). Earlier experiments showed that this molecule may play a role in circuit formation in vitro (Keller et al., 1989). Most recently, results suggested that there is a correlation between the early commitment of the cortex to this molecular phenotype and the formation of specific thalamocortical connections (Barbe and Levitt, submitted; Appendix II). These experiments have led to additional issues for exploration of cortical commitment and connectivity. Using a tissue transplantation paradigm, I will be testing two aspects of the development of the cortex into functional areal arrays: 1) The commitment of cortical neurons to a functional areal phenotype is linked to the cell cycle. 2) The connections induced between limbic thalamic afferents and LAMP- positive cortical transplants are maintained permanently. The long term goals of my laboratory, some of which are addressed in this proposal, are to better understand the molecular factors that modulate the assembly of functional neuronal circuits, both during development and after injury of the mammalian central nervous system.
