Altered short-term hippocampal synaptic plasticity in mutant alpha-synuclein transgenic mice.
Hippocampal synaptic plasticity was studied in transgenic mice over-expressing human alpha-synuclein containing the A30P Parkinson's disease mutation. Medial perforant path-dentate granule cell synapses showed enhanced paired-pulse depression (PPD) for short interpulse intervals (< 200 ms), without differences in basal transmission. Extracellular calcium reduction failed to rescue the enhanced PPD. Paired-pulse facilitation in the CA1 region was normal in slices from transgenic mice, but enhanced synaptic depression was revealed upon repetitive stimulation of the Schaffer collaterals. Long-term potentiation in the CA1 field was not impaired in slices from transgenic mice. These results suggest that mutant alpha-synuclein accumulation impairs short-term changes in synaptic strength when neurotransmitter availability is limited due to enhanced release probability or repetitive synaptic activity.
Steidl
Jill V
JV
Department of Neuroscience, The University of Minnesota, 6-145 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
Gomez-Isla
Teresa
T
Mariash
Ami
A
Ashe
Karen Hsiao
KH
Boland
Linda M
LM
D000818:Animals; D006224:Cricetinae; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein