Fig. 1

J20 mice exhibit Ca²⁺-permeable AMPA receptors. a Current-voltage (I/V) relationship of synaptic responses at holding potentials of -70, -40, -20, 0, +20 and +40 mV in WT, GluA2^G/G, J20 and GluA2^G/G/J20 mice normalized to evoked EPSC amplitude at -60 mV revealed inward rectification in J20 mice (n’s; WT = 8, GluA2^G/G = 5, J20 = 8, GluA2^G/G/J20 = 5). The rectification index (RI), ratio of EPSC amplitudes at -60 mV and +40 mV, also confirmed a significantly larger inward current in J20 animals compared to all other genotypes. The representative waveforms for the WT group are absolute amplitude as per the scale bar. Representative waveforms for all other groups at both holding potentials are scaled equally to equate the +40 mV response with the WT +40 mV response. The dashed line indicates the peak amplitude of the WT -60 mV response. b The addition of NASPM, a Ca²⁺-permeable AMPAR antagonist, evoked linear I-V relationships in all four genotypes (n’s; WT = 4, GluA2^G/G = 4, J20 = 5, GluA2^G/G/J20 = 5). Waveforms are as for panel a. c Representative Co²⁺ labelling images of the CA1 hippocampal region from WT, GluA2^G/G, J20 and GluA2^G/G/J20 mice. Kainate-induced Co²⁺ loading revealed a significant increase in the uptake of CoCl² in acute slices taken from J20 mice, indicative of an increase in Ca²⁺-permeable AMPARs (n’s; WT = 10, GluA2^G/G = 8, J20 = 9, GluA2^G/G/J20 = 8). Each value represents the mean ± the SD for bar graphs and SEM for line graphs. *p < 0.05, ***p < 0.001, ****p < 0.0001