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 journalArticle

1183 Citations (Scopus)

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(-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
JournalNeuron
Volume25
Issue number1
StatePublished - Jan 2000
Externally publishedYes

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Synucleins
Dopamine
Corpus Striatum
Amphetamine
Synaptic Transmission
Synapses
Electric Stimulation
Parkinson Disease
Brain
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., ... Rosenthal, A. (2000). Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron, 25(1), 239-252.

Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. / Abeliovich, Asa; Schmitz, Yvonne; Fariñas, Isabel; Choi-Lundberg, Derek; Ho, Wei Hsien; Castillo, Pablo E.; Shinsky, Natasha; Garcia Verdugo, Jose Manuel; Armanini, Mark; Ryan, Anne; Hynes, Mary; Phillips, Heidi; Sulzer, David; Rosenthal, Arnon.

In: Neuron, Vol. 25, No. 1, 01.2000, p. 239-252.

Research output: Contribution to journalArticle

Abeliovich, A, Schmitz, Y, Fariñas, I, Choi-Lundberg, D, Ho, WH, Castillo, PE, Shinsky, N, Garcia Verdugo, JM, Armanini, M, Ryan, A, Hynes, M, Phillips, H, Sulzer, D & Rosenthal, A 2000, 'Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system', Neuron, vol. 25, no. 1, pp. 239-252.
Abeliovich A, Schmitz Y, Fariñas I, Choi-Lundberg D, Ho WH, Castillo PE et al. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron. 2000 Jan;25(1):239-252.
Abeliovich, Asa ; Schmitz, Yvonne ; Fariñas, Isabel ; Choi-Lundberg, Derek ; Ho, Wei Hsien ; Castillo, Pablo E. ; Shinsky, Natasha ; Garcia Verdugo, Jose Manuel ; Armanini, Mark ; Ryan, Anne ; Hynes, Mary ; Phillips, Heidi ; Sulzer, David ; Rosenthal, Arnon. / Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. In: Neuron. 2000 ; Vol. 25, No. 1. pp. 239-252.
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