Role of α-synuclein in synaptic glutamate release

Defective mobilization of dopamine from the reserve pool has been reported in both α-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 α-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 α-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 α-synuclein impairs mobilization of glutamate from the reserve pool. However, transgenic expression of A30P mutated or wild type α-synuclein does not appear to prevent endogenous mouse α-synuclein to carry out this function.