NEURON GLIAL INTERACTIONS DURING THE IN-VIVO AND IN-VITRO DEVELOPMENTOF THE NIGROSTRIATAL CIRCUIT

This paper examines a particular aspect of glial-neuronal interactions during central nervous system development: the possible influence of growing neurites on the expression of glial-associated extracellular m atrix (ECM) molecules. In particular, using in vivo manipulations of t he dopaminergic projections from the midbrain substantia nigra, as wel l as an in vitro model of the developing nigrostriatal circuit, we loo k at the reciprocal interactions between growing dopaminergic axons an d astrocyte-derived ECM molecules in the striatum. Glial-derived glyco conjugates, including tenascin and a proteoglycan designated DSD-1, ar e developmentally expressed ECM molecules which have been shown to hav e different effects on immature neurons and their growing processes. H ere we show that the glial expression of these ECM constituents in a t arget region (the caudate-putamen or neostriatum) may be affected by t he presence or absence of an appropriate, maturing afferent projection (in this case, dopaminergic nigrostriatal axons). In general, our res ults reveal complex glial-neuronal interactions during the normal deve lopment of central nervous system circuits, and the ability to create in vivo and in vitro models which may be useful toward understanding t hese complex cellular and molecular interactions in degeneration and p lasticity of the nigrostriatal circuit in diseases including Parkinson 's.