Fig. 5

The GLT-1 contribution to glutamate clearance at postsynaptic microenvironments is elevated in 3xTg mice compared to WT. A Average postsynaptic iGluSnFR response to 5 (left) and 100 pulses (right) of electrical stimulation (100 Hz) in WT (top; black and grey) and 3xTg mice (bottom; orange and grey) before and after DHK application. Grey traces denote average iGluSnFR response before DHK application. B GLT-1 decay ratio in WT and 3xTg mice, calculated by the fold increase in iGluSnFR decay induced by a saturating concentration of the GLT-1 inhibitor DHK. C Representative images depicting the postsynaptic iGluSnFR response in the presence of DHK in WT (top row) and 3xTg (bottom row) mice evoked by 100 pulses of electrical stimulation (100 Hz). D Average postsynaptic iGluSnFR responses to 5 (left) and 100 pulses (right) of stimulation in WT-saline (black), 3xTg saline (orange), WT-ceftriaxone (Cef; blue), and 3xTg-ceftriaxone-treated mice (pink). E iGluSnFR decay tau in saline- or ceftriaxone-treated WT and 3xTg mice. F Representative images depicting the postsynaptic iGluSnFR response in WT-saline (top row), 3xTg-saline (second row), WT-ceftriaxone (third row), and 3xTg-ceftriaxone-treated mice (bottom row) evoked by 100 pulses of electrical stimulation (100 Hz). Black lines above iGluSnFR traces indicate the timing and duration of electrical stimulation. Scale bars in A: 10%ΔF/F, 500 ms (left) and 25%ΔF/F, 1000 ms (right). DHK traces scaled to match the peak of control (without DHK) traces. Scale bar in E: 10 µm. Scale bars in D: 10%ΔF/F, 200 ms (left) and 25%ΔF/F, 500 ms (right). 3xTg traces scaled to match the peak of WT traces. Error bars indicate s.e.m. *** p < 0.001