Impairment in hippocampal long-term potentiation in mice under-expressing the Alzheimer's disease related gene presenilin-1.
Presenilin-1 (PS1) is intimately involved in cleavage of amyloid precursor protein to form beta-amyloid peptides, certain forms of which aggregate in the brains of patients with Alzheimer's disease (AD). The function(s) of PS1 and its precise involvement in the development of cognitive deficits associated with AD are unclear. We have utilised genetically modified mice that under-express PS1 (PS1(+/-) mice) to investigate the role of PS1 in hippocampal synaptic plasticity. Field excitatory postsynaptic responses elicited by baseline stimulation were indistinguishable between PS1(+/-) mice and wild-type controls. Likewise, a measure of short-term plasticity, paired-pulse facilitation, was normal in PS1(+/-) mice. However, long-term potentiation induced by multiple tetanus trains was reduced in PS1(+/-) animals. These results demonstrate that chronic reduction of PS1 activity leads to impaired synaptic plasticity, thus suggesting a role for PS1 in normal cognitive function.
Morton
Robin A
RA
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University of Walk, Bristol BS8 1TD, UK.
Kuenzi
Frederick M
FM
Fitzjohn
Stephen M
SM
Rosahl
Thomas W
TW
Smith
David
D
Zheng
Hui
H
Shearman
Mark
M
Collingridge
Graham L
GL
Seabrook
Guy R
GR
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D053764:Presenilin-1; D021381:Protein Transport / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D008565:Membrane Proteins; D053764:Presenilin-1; D011956:Receptors, Cell Surface