Neuron—Glial interactions during the in vivo and in vitro development of 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 matrix (ECM) molecules. In particular, using in vivo manipulations of the dopaminergic projections from the midbrain substantia nigra, as well as an in vitro model of the developing nigrostriatal circuit, we look at the reciprocal interactions between growing dopaminergic axons and astrocyte-derived ECM molecules in the striatum. Glial-derived glycoconjugates, including tenascin and a proteoglycan designated DSD-1, are developmentally expressed ECM molecules which have been shown to have different effects on immature neurons and their growing processes. Here we show that the glial expression of these ECM constituents in a target region (the caudate-putamen or neostriatum) may be affected by the presence or absence of an appropriate, maturing afferent projection (in this case, dopaminergic nigrostriatal axons). In general, our results reveal complex glial-neuronal interactions during the normal development of central nervous system circuits, and the ability to create in vivo and in vitro models which may be useful toward understanding these complex cellular and molecular interactions in degeneration and plasticity of the nigrostriatal circuit in diseases including Parkinson's.