Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system

Asa Abeliovich, Yvonne Schmitz, Isabel Fariñas, Derek Choi-Lundberg, Wei Hsien Ho, Pablo E. Castillo, Natasha Shinsky, Jose Manuel Garcia Verdugo, Mark Armanini, Anne Ryan, Mary Hynes, Heidi Phillips, David Sulzer, Arnon Rosenthal

Research output: Contribution to journalArticlepeer-review

1437 Scopus citations


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(-1-) 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.

Original languageEnglish (US)
Pages (from-to)239-252
Number of pages14
Issue number1
StatePublished - Jan 2000
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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