Fig. 2

Age-dependent alteration of protein degradation mechanisms that support LTD formation. a–f The effects of several protein degradation blockers on LTD were examined in hippocampus slices from 4- to 8-month old adult a–c and 20- to 24-month old aged d–f mice. After being sliced, each slice was placed in a chamber filled with aCSF containing 20 μM picrotoxin and incubated for 3 h at 33 °C. Slices were then exposed to the following blockers or vehicle control (veh) in aCSF with picrotoxin for 30 min before the start of LFS (900 pulses, 1 Hz): 0.1 μM MG132 a, d, 1 mM 3MA b, e, and 0.1 μM Bafilomycin c, f. In this experiment, we used a 900-pulse protocol for LTD induction, which led to the formation of stable LTD in slice preparations (data not shown), to avoid any reduction in sensitivity to chemicals that would result from saturated LTD. In control experiments, these concentrations did not directly change the field excitatory postsynaptic potential (fEPSP) size (data not shown). Each graph shows temporal change in normalized fEPSP slop before and after LFS application. Data are shown as the mean ± SEM. g–i The effect of LFS on fEPSP was statistically analyzed based on the average data obtained from 59 to 60 min in the absence and presence of MG132 g, 3MA h, and Bafilomycin i. **p < 0.01, unpaired t-test. Data are shown as the mean ± SEM. The number of slices used in each group is shown in parentheses above each column