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Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn-/- mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn-/- mice display a standard pattem of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn-/- mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission. Neuron 2000 Jan;25(1):239-52 Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A Department of Neurology, University of California, San Francisco 94143, USA. PMID: 10707987, UI: 20170260 http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10707987&form=6&db=m&Dopt=b janet paterson 53 now / 41 dx / 37 onset a new voice: http://www.geocities.com/janet313/ 613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0