Synaptic transmission and hippocampal long-term potentiation in transgenicmice expressing FAD-linked presenilin 1

Mutations in two related genes, presenilin 1 acid presenilin 2 (PS1 and PSZ ), cause a subset of early-onset familial Alzheimer's disease (FAD). PS1 is expressed in a variety of neuronal and peripheral tissues, including neuro nal populations known to be at risk in Alzheimer's disease such as CA1 hipp ocampal neurons. To examine whether FAD-linked mutations in PS1 directly in fluence the physiology of learning and memory, we measured the field excita tory postsynaptic potential (fEPSP) at the Schaffer collateral-CA1 synapse in hippocampal slices. Basal synaptic transmission and long-term potentiati on (LTP) were examined in neurons of transgenic mice expressing wild-type h uman PS1 (WtTg) and FAD-linked A246E PS1 variant (MTg) and in neurons of no ntransgenic littermates (NTg). Several measures of basal synaptic transmiss ion were unaltered in WtTg and MTg compared to NTg mice, including maximum fEPSP slope, maximum fEPSP amplitude, maximum fiber volley amplitude, and t he function relating fiber volley amplitude to fEPSP slope, an index of bas al synaptic strength. In addition, paired-pulse facilitation was not change d. However, upon theta burst stimulation or high-frequency stimulation, inp ut-specific LTP in MTg animals had a larger initial amplitude and was more persistent than that in WtTg or NTg animals. These data suggest that the FA D-linked A246E variant of PS1 leads to higher degree of LTP induction in mi ce. (C) 1999 Academic Press.