Figure 7. Blockade of tonic inhibition rescued deficits in LTP and working memory in 5xFAD mice.
(a) Hippocampal slice recordings revealed LTP impairment in the DG of 5xFAD mice (gray), compared to the control animals (green). Blocking tonic inhibition by L-655,708 (100 nM, orange) or SNAP-5114 (50 μM, blue) rescued the impairment of LTP. (b) Quantified potentiation within 50–60 min after high frequency stimulation in various conditions. Two-way ANOVA revealed a significant change among genotype and drug treatments (F (2, 56) = 3.7, P<0.04), numbers in histograms indicate number of slices. (c) Y-maze test showed significant impairment of spontaneous alternation behavior in 5xFAD mice (gray) compared to WT animals (green). Chronic block of tonic inhibition by repeated injection of L-655,708 or SNAP-5114 for one week rescued the behavioral deficit. (d) The total number of arm entries was not different among WT, 5xFAD, 5xFAD+L-655,708, and 5xFAD+SNAP-5114 groups, Numbers in histograms (c & d) indicate number of mice. Data are presented as mean ± s.e.m., * P < 0.05, ** P < 0.01.