2004 Nature Pub lishing Group http://www

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. com/natureneuroscience the axon terminals in the striatum (Fig. 1d) or through the lateral ventricular route. Once rescued, the nigral cells survive for months after the withdrawal of GDNF, indicating that they may not be dependent on GDNF for further survival8. Tests of spontaneous and drug-induced motor behavior in rats that were subjected to intrastriatal 6-OHDA lesions stress the importance of the GDNF application. Protection of the nigral dopamine cell bodies alone, in the absence of axons projecting to the striatum, as seen after injection of GDNF into the substantia nigra or the lateral ventricle, is insufficient to provide either protection against or recovery from lesion-induced motor deficits11. When GDNF is applied in the striatum at the time of lesion, by contrast, the entire nigrostriatal pathway is preserved and the animals retain their performance in both druginduced and spontaneous motor tests7. Other studies, performed in vitro, indicate that neurotrophic factors may elicit different responses with respect to axonal growth and survival when applied locally at the axon or cell body12. It seems possible, therefore, that the nigral dopaminergic neurons may respond differently to GDNF when it is applied at their cell bodies or close to their axons within the striatum.