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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<jats:italic>GDNF<\/jats:italic>mRNA was present in neonates but markedly increased during the first 2\u20133 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.<jats:italic>GDNF<\/jats:italic>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 (PV+) interneurons, which only represent \u223c0.7% of all striatal neurons. The remaining 5% of GDNF+ cells are cholinergic and somatostatin+ interneurons. Surprisingly, medium spiny projection neurons (MSNs), the vast majority of striatal neurons that receive a strong DA innervation, do not express GDNF. PV+ interneurons constitute an oscillatory functional ensemble of electrically connected cells that control MSNs' firing. Production of GDNF in the PV+ neurons might be advantageous to supply synchronous activity-dependent release of GDNF in broad areas of the striatum. Stimulation of the GDNF-producing striatal PV+ ensemble in PD patients could have therapeutic effects.<\/jats:p>","DOI":"10.1523\/jneurosci.2693-11.2012","type":"journal-article","created":{"date-parts":[[2012,1,18]],"date-time":"2012-01-18T19:02:25Z","timestamp":1326913345000},"page":"864-872","source":"Crossref","is-referenced-by-count":90,"title":["GDNF Is Predominantly Expressed in the PV+ Neostriatal Interneuronal Ensemble in Normal Mouse and after Injury of the Nigrostriatal 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