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 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, 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.
Pubmed ID: 10707987 RIS Download
Amphetamine | Animals | Autoreceptors | Calbindins | Calcium | Corpus Striatum | Dopamine | Dopamine Agents | Female | Gene Expression | Glutamic Acid | Hippocampus | Locomotion | Long-Term Potentiation | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Motor Activity | Nerve Tissue Proteins | Neurons | Presynaptic Terminals | S100 Calcium Binding Protein G | Substantia Nigra | Synaptic Transmission | Synucleins | alpha-Synuclein | rab3A GTP-Binding Protein