The role of mitochondrial porins and the permeability transition pore in learning and synaptic plasticity.
Mitochondrial outer membrane permeability is conferred by a family of porin proteins. Mitochondrial porins conduct small molecules and constitute one component of the permeability transition pore that opens in response to apoptotic signals. Because mitochondrial porins have significant roles in diverse cellular processes including regulation of mitochondrial ATP and calcium flux, we sought to determine their importance in learning and synaptic plasticity in mice. We show that fear conditioning and spatial learning are disrupted in porin-deficient mice. Electrophysiological recordings of porin-deficient hippocampal slices reveal deficits in long and short term synaptic plasticity. Inhibition of the mitochondrial permeability transition pore by cyclosporin A in wild-type hippocampal slices reproduces the electrophysiological phenotype of porin-deficient mice. These results demonstrate a dynamic functional role for mitochondrial porins and the permeability transition pore in learning and synaptic plasticity.
Weeber
Edwin J
EJ
Division of Neuroscience, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Levy
Michael
M
Sampson
Margaret J
MJ
Anflous
Keltoum
K
Armstrong
Dawna L
DL
Brown
Sarah E
SE
Sweatt
J David
JD
Craigen
William J
WJ
D000818:Animals; D001483:Base Sequence; D016572:Cyclosporine / Q000494:pharmacology; D017931:DNA Primers; D005260:Female; D006624:Hippocampus / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018272:Porins / Q000235:genetics / Q000502:physiology*; D050994:Voltage-Dependent Anion Channels
D017931:DNA Primers; D018272:Porins; D050994:Voltage-Dependent Anion Channels; D016572:Cyclosporine