Neuron
Volume 25, Issue 1, January 2000, Pages 239-252
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Article
Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System

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Abstract

α-Synuclein (α-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 α-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 α-Syn−/− mice display a standard pattern 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, α-Syn−/− mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that α-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.

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