Article Figures & Data
Figures
- Figure 1.
PcTX1, a selective inhibitor of ASIC1a and ASIC1a/2b channels, had no effect on LTP at SC-CA1 synapses. A, Inset, Representative ASIC-like current traces in the control (Ctrl, black) and after application of 1 and 30 nm PcTX1 (gray). Data were fitted to a single Hill equation with IC50 = 1.36 nm (Hill coefficient, 1.5). Each point represented the average from 6–13 experiments. B, High-frequency stimulation (four trains)-induced LTP was not impaired by high concentration of PcTX1 (30 nm, n = 6, 5 animals) as compared with the Ctrl (n = 7, 7 animals). C, Summary of LTP induced by different induction protocols in Ctrl (HFS × 1, n = 5, 5 animals; HFS × 4, n = 7, 7 animals) and in the presence of PcTX1 (HFS × 1, n = 6, 5 animals; HFS × 4, n = 6, 5 animals); ns, not significantly different.
- Figure 2.
Genetic ablation of ASIC1a did not impair LTP at SC-CA1 synapses. A, A schematic diagram describing the gene targeting strategy and deletion of exons 2 and 3 of ASIC1a gene using the Cre/loxP recombination system. B, RT-PCR with whole-brain mRNA from a WT (+/+) littermate and ASIC1a heterozygous (+/−) and homozygous (−/−) KO mice. GAPDH was used as the control. C, Example traces of ASIC-like currents (top) recorded from nucleated patches isolated from interneurons in stratum oriens alveus of WT (+/+; n = 8, 4 animals), heterozygous (+/−; n = 8, 4 animals), and homozygous (−/−; n = 8, 4 animals) mice for ASIC1a deletion and the summary (bottom). Schematic of fast application of proton (pH = 5) on a nucleated patch is shown. D, Example traces of ASIC-like currents (top) recorded from CA1 pyramidal neurons of WT (+/+; n = 5, 2 animals) and homozygous (−/−, n = 6, 2 animals) mice for ASIC1a deletion and the summary (bottom). Schematic of puff application of proton (pH = 5) on a CA1 pyramidal neuron in the slice is shown. E, SC-CA1 input/output curves of slices from control (WT, ASIC1a+/+) littermates (filled circles; n = 6, 4 animals) and ASIC1a-null (ASIC1a−/−) mice (open circles; n = 4, 2 animals). F, HFS (two trains)-induced LTP was not impaired in slices from ASIC1a−/− mice (n = 5, 4 animals) compared to that from WT littermates (n = 5, 4 animals). G, Summary of LTP induced by different LTP-induction protocols in WT littermates (HFS × 1, n = 5, 4 animals; HFS × 2, n = 5, 4 animals) and ASIC1a-null mice (HFS × 1, n = 5, 4 animals; HFS × 2, n = 5, 4 animals).
- Figure 3.
ASIC1a-null mice performed the spatial learning task as well as WT mice. A, Learning curves during spatial training in the hidden platform of the Morris water maze. The latency for each mouse to reach the hidden platform was recorded (ASIC1a+/+, n = 14; ASIC1a−/−, n = 6). B, Top, representative swim traces. T, Target zone; R, right; O, opposite; L, left of target. Bottom, Percent time spent in T zone and other zones during the probe trials (ASIC1a+/+, n = 14; ASIC1a−/−, n = 6). **p < 0.005; ***p < 0.001.
