Figure 7: EAAT2 overexpression by ceftriaxone treatment impairs STDP.
From: Astrocytes gate Hebbian synaptic plasticity in the striatum
(a) Experimental design: ceftriaxone (or saline) was daily injected for 8 days; electrophysiology and immunohistochemistry experiments were performed 24 h after the last injection. (b) Immunohistochemistry revealed an increase of EAAT2-positive puncta in striatal slices from ceftriaxone-injected rats than in slices from saline-injected rats. Scale bar: 10 μm. (c) Example of LTP induced by 100 post–pre pairings recorded in a saline-injected rat (ΔtSTDP=−18 ms). Top, EPSC strength before and after pairings. Bottom, time course of Ri (baseline: 50±0.2 MΩ; 50–60 min after pairings: 48±0.2 MΩ; change of −5%). (d) Example of LTD induced by 100 pre–post pairings recorded in a saline-injected rat (ΔtSTDP=+13 ms; Ri, baseline: 60±0.3 MΩ; 50–60 min after pairings: 61±0.4 MΩ; change of 0.4%). (e) Averaged time-course of experiments performed in saline-injected rats, showing bidirectional STDP: LTP was induced for post–pre (−30<ΔtSTDP<0 ms) and LTD for pre–post (0<ΔtSTDP<+30 ms) pairings. (f) Example of the lack of plasticity observed with 100 post–pre pairings (ΔtSTDP=−10 ms) recorded from a ceftriaxone-treated rat. Top, EPSC strength was not significantly different before and after pairings. Bottom, time course of Ri (baseline: 75±0.3 MΩ; 40–50 min after pairings: 69±0.5 MΩ; change of −8%). (g) Example of the absence of plasticity observed with 100 pre–post pairings (ΔtSTDP=+10 ms) from a ceftriaxone-treated rat. EPSC strength did not differ significantly before and after pairings (Ri, baseline: 149±0.6 MΩ; 40–50 min after pairings 163±10 MΩ; change of 10%). (h) Averaged time course of experiments performed on ceftriaxone-treated rats, showing an absence of STDP for both post–pre and pre–post pairings. (i) Time window for long-term synaptic strength for post–pre and pre–post pairings (−30<ΔtSTDP<+30 ms) in saline- and ceftriaxone-treated rats. Synaptic strength was assessed 45–60 min after pairings (empty and pink circles: individual neurons; gray or purple circles: average). Bidirectional plasticity was induced in saline-injected rats, whereas no plasticity was observed in ceftriaxone-treated rats. Insets correspond to the average of 60 EPSCs during baseline and at 1 h after STDP pairings. Error bars represent the s.d. (except in panel b,i: s.e.m.). *P<0.05; **P<0.01; ***P<0.001; NS: not significant by unpaired t-test, two-tailed (b–d,f,g) or one sample t-test (e,h,i).
