Role of alpha-synuclein in synaptic glutamate release.
Defective mobilization of dopamine from the reserve pool has been reported in both alpha-synuclein knockout mice (KO) and pPrp-A30P transgenic mice. The present study extends these findings to glutamate release. Standard hippocampal slices were prepared from KO, pPrp-A30P, and C57BL/6J wild type (WT1) mice, as well as from mice with transgenic overexpression of wild type human alpha-synuclein (pSyn-hASY) and their negative littermates (WT2), and field responses were measured in CA3 in response to mossy fiber stimulation. The input/output curves indicated no differences in basal synaptic transmission between groups. Paired-pulse facilitation was significantly weaker in both transgenic alpha-synuclein lines and KO mice compared to their controls. High-frequency stimulation induced LTP only in transgenic mice. Frequency-facilitation was absent in KO mice and different from other mouse lines. These findings support the idea that lack of alpha-synuclein impairs mobilization of glutamate from the reserve pool. However, transgenic expression of A30P mutated or wild type alpha-synuclein does not appear to prevent endogenous mouse alpha-synuclein to carry out this function.
Gureviciene
Irina
I
Department Neurobiology, A. I. Virtanen Institute for Molecular Science, University of Kuopio, P.O. Box 1627/Neulaniementie 2, FIN-70211 Kuopio, Finland. Irina.Siverina@uku.fi
Gurevicius
Kestutis
K
Tanila
Heikki
H
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D051844:alpha-Synuclein; D018698:Glutamic Acid