Figure 3.

Severe impairment in synaptic transmission between hippocampal CA3 and CA1 cells in APP_Ind mice (line H6). (a) The responsiveness of CA1 cells to increasing afferent fiber stimulation [slope of input–output (i/o) relation; see Materials and Methods] was determined in APP_Ind mice and nontransgenic controls to assess the strength of basal synaptic transmission. Each data point represents average results obtained in 17–87 slices obtained from 4–15 mice. For each age group, results were normalized to the mean value obtained in nontransgenic mice. Statistically significant differences were identified by Duncan’s test between transgenic and nontransgenic mice (P < 0.05 at 3–4 weeks; P < 0.01 at 2–4 and 8–10 months) and between 2- to 4-month-old and 8- to 10-month-old transgenic mice (P < 0.01). (b) Representative field EPSPs at increasing stimulus strengths are shown for a nontransgenic and an APP_Ind mouse, illustrating that far higher stimulation strengths are required to elicit synaptic responses in APP_Ind mice. The fiber volley (arrow) is an indirect measure of the number of axons activated. (c and d) Paired-pulse facilitation (PPF) and quantal size were measured in CA1 cells of 8- to 10-month-old APP_Ind mice and nontransgenic controls. Each column represents average results from 6–8 hippocampal slices prepared from 2–4 mice. Paired-pulse facilitation was expressed as the ratio (α₂/α₁) of the average amplitudes of EPSCs evoked by a pair of closely spaced stimuli (c). Quantal size was determined as the mean amplitude of miniature EPSCs (mEPSCs) (d). pA, picoamps.