STRIATAL TARGET-INDUCED AXONAL BRANCHING OF DOPAMINERGIC MESENCEPHALIC NEURONS IN CULTURE VIA DIFFUSIBLE FACTORS

The effects of striatal target cells on the morphological development of dopaminergic neurons were studied in dissociated cultures of embryo nic rat mesencephalon. Mesencephalic neurons were cultured for four da ys in presence of target striatal cells or non target cerebellar ones, The outgrowth of dopaminergic neurons, visualized after tyrosine hydr oxylase immunohistochemistry was examined by quantitative morphometry. In cocultures, the increased complexity of dopaminergic neurites (bra nching) was the most striking pattern, It was dependent on the presenc e of target striatal cells as compared to non target ones, Cultures ra ised in presence or absence of serum lead to suggest the implication o f striatal neurons rather than glia, Using MAP2 and phosphorylated neu rofilaments immunohistochemistry in combination with tyrosine hydroxyl ase immunolabelling, it could be shown that the target-induced branchi ng effect concerned only axonal and not dendritic processes, To furthe r define whether diffusible factors from the striatal target would par ticipate in the axonal branching effect, mesencephalic cells were cult ured in conditioned medium from striatal neurons, Striatal conditioned medium enhanced dopamine uptake and dopamine neuron branching to the same extent as that observed in striatal cocultures, These findings de monstrate that soluble factors secreted by striatal neurons themselves selectively influence the branching of dopaminergic axons in vitro. ( C) 1997 Wiley-Liss, Inc.