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The Journal of Neuroscience, December 8, 2004, 24(49):11165-11170; doi:10.1523/JNEUROSCI.2559-04.2004

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Neurobiology of Disease
Role of -Synuclein in Presynaptic Dopamine Recruitment

Leonid Yavich,^1,2 Heikki Tanila,^2,4 Saila Vepsäläinen,^2,3 and Pekka Jäkälä^2,4

Departments of ¹Pharmacology and Toxicology and ²Neuroscience and Neurology and ³Brain Research Unit, Clinical Research Centre/Mediteknia, University of Kuopio, and ⁴Department of Neurology, University Hospital of Kuopio, FIN-70211 Kuopio, Finland

Real-time monitoring of stimulated dopamine release in mice with different -synuclein expression was used to study the role of -synuclein in presynaptic dopamine recruitment. Repeated electrical stimulations of ascending dopaminergic pathways decreased the capacity of the readily releasable pool (RRP) and temporarily increased its refilling rate, significantly slowing the rate of dopamine decline in mice with normally expressed -synuclein. Mice with -synuclein null mutation demonstrated a permanent increase of the refilling rate. This increase maintained stable dopamine release during stimulation (which induced dopamine decline in other animals) and served as an adaptation to altered dopamine compartmentalization. Mice without -synuclein and with overexpression of human A30P mutated -synuclein had a lower capacity of the dopamine storage pool than other animals. Reducing capacity of the storage pool in transgenic A30P mice led to paradoxical effects of L-dopa, which elevated dopamine release in response to single stimulation but decreased the refilling rate of the RRP.

Key words: dopamine; storage; -synuclein; null mutation; A30P transgenic mice; in vivo voltammetry

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Received June 28, 2004; revised October 17, 2004; accepted October 20, 2004.

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