Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer’s disease mutation is normalized with a benzodiazepine

Shahid H. Zaman, Angèle Parent, Aaron Laskey, Michael K. Lee, David R. Borchelt, Sangram S. Sisodia, Roberto Malinow

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Mutations in presenilin 1 (PS1) are the most common causes of familial Alzheimer's disease (FAD). We examined synaptic physiology in hippocampal brain slices of transgenic mice expressing the FAD-linked PS1 deletion of exon 9 variant. Basal excitatory transmission and paired-pulse facilitation in PS1 mutant mice were unchanged. Short- and long-term potentiation of excitatory transmission following high-frequency stimulation were greater in transgenic mice expressing mutant PS1. Mutants had enhanced synaptic inhibition, which may be a compensatory change offsetting an abnormally sensitized plasticity of excitatory transmission. Increasing inhibitory transmission in mutant animals even more with a benzodiazepine reverted synaptic potentiation to the levels of controls. These results support the potential use of benzodiazepines in the treatment of familial Alzheimer's disease. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)54-63
Number of pages10
JournalNeurobiology of Disease
Volume7
Issue number1
DOIs
StatePublished - Feb 2000

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