Role of alpha-synuclein in synaptic glutamate release

Neurobiol Dis. 2007 Oct;28(1):83-9. doi: 10.1016/j.nbd.2007.06.016. Epub 2007 Jun 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mossy Fibers, Hippocampal / metabolism*
  • Mutation
  • Neuronal Plasticity / physiology*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Synapses / metabolism*
  • Synaptic Transmission / physiology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein
  • Glutamic Acid