Altered hippocampal synaptic physiology in aged parkin-deficient mice.
We examined synaptic function in the hippocampus of aged mice deficient for the Parkinson's disease-linked protein, parkin. Surprisingly, heterozygous but not homozygous parkin-deficient mice exhibited impairments in basal excitatory synaptic strength. Similarly heterozygous mice exhibited broad deficits in paired-pulse facilitation, while homozygous parkin-deficient mice exhibited more restricted deficits. In contrast to the measurements of basal synaptic function, synaptic plasticity was not altered in aged heterozygous parkin-deficient mice, but was enhanced in aged homozygous parkin-deficient mice, due to an absence of age-related decline. These findings of differential synaptic phenotypes in heterozygous vs. homozygous parkin deficiency suggest compensatory responses to genetic abnormalities could play an important role during the development of pathology in response to parkin deficiency.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. hanson.jesse@gene.com
Jesse E
JE
Hanson
Adrienne L
AL
Orr
Daniel V
DV
Madison
D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein