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Glial cell line-derived neurotrophic factor (GDNF) is absolutely required for survival of dopaminergic (DA) nigrostriatal neurons and protect them from toxic insults. Hence, it is a promising, albeit experimental, therapy for Parkinson's disease (PD). However, the source of striatal GDNF is not well known. GDNF seems to be normally synthesized in neurons, but numerous reports suggest GDNF production in glial cells, particularly in the injured brain. We have studied in detail striatal GDNF production in normal mouse and after damage of DA neurons with MPTP. Striatal GDNF mRNA was present in neonates but markedly increased during the first 2-3 postnatal weeks. Cellular identification of GDNF by unequivocal histochemical methods demonstrated that in normal or injured adult animals GDNF is expressed by striatal neurons and is not synthesized in significant amounts by astrocytes or microglial cells. GDNF mRNA expression was not higher in reactive astrocytes than in normal ones. Approximately 95% of identified neostriatal GDNF-expressing cells in normal and injured animals are parvalbumin-positive (PVϩ) interneurons, which only represent ϳ0.7% of all striatal neurons. The remaining 5% of GDNFϩ cells are cholinergic and somatostatinϩ interneurons. Surprisingly, medium spiny projection neurons (MSNs), the vast majority of striatal neurons that receive a strong DA innervation, do not express GDNF. PVϩ interneurons constitute an oscillatory functional ensemble of electrically connected cells that control MSNs' firing. Production of GDNF in the PVϩ neurons might be advantageous to supply synchronous activity-dependent release of GDNF in broad areas of the striatum. Stimulation of the GDNF-producing striatal PVϩ ensemble in PD patients could have therapeutic effects.

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13This contribution illustrates the advantages of integrating conventional 14 geomorphological methods with InSAR, ground penetrating radar and trenching for 15 sinkhole mapping and characterization in a mantled evaporite karst area, where a 16 significant proportion of the karstic depressions have been obliterated by artificial fills. 17The main practical aim of the investigation was to elucidate whether buried sinkholes 18 overlap the areas planned for the construction of buildings and services, in order to 19 apply a preventive planning strategy. Old aerial photographs and detailed topographic 20 maps were the most useful sources of information for the identification of sinkholes and 21helped to obtain information on their chronology, either a minimum age or bracketing 22

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