Figure 2.

Modulation of long-term synaptic plasticity by EAATs. (A) Pharmacological inhibition of EAATs by the broad-spectrum non-transportable blocker threo-β-benzyloxyaspartic acid (TBOA) increases the magnitude of long-term depression (LTD) in cerebellar Purkinje cells, triggered by high frequency stimulation (HFS) of the parallel fibers (five pulses at 100 Hz) paired with Purkinje cell depolarization (0 mV for 50 ms) repeated at 0.5 Hz for 1 min. This LTD is mGluR1-dependent since it is inhibited by LY367385. Adapted with permission from Brasnjo and Otis (2001). (B) Genetic deletion of EAAT2 decreases the amplitude of HFS-induced long-term potentiation (LTP) in the stratum radiatum region of the hippocampus. Adapted with permission from Katagiri et al. (2001). (C) Specific pharmacological blockade of EAAT2 with dihydrokainic acid (DHK) results in a broadening of the permissive window for spike-timing dependent plasticity (STDP) expression at corticostriatal synapses. Inhibition of EAAT2 results in t-LTD or t-LTP at temporal intervals where no plasticity is observed under control conditions (beyond Δt_STDP = ±30 ms). (C1) Time window (Δt_STDP) for long-term synaptic strength for post-pre and pre-post pairings. (C2) Averaged time-course of experiments with transient blockade of EAAT2 with bath-application of DHK for post-pre and pre-post pairings beyond Δt_STDP = ±100 ms. Adapted with permission from Valtcheva and Venance (2016). (D) Overexpression of EAAT2 by chronic ceftriaxone treatment prevents the expression of low frequency stimulation (LFS)-induced LTD at the hippocampal mossy fibers-CA3 synapse. Adapted with permission from Omrani et al. (2009). (E) STDP time window (Δt_STDP) for long-term synaptic strength for post-pre and pre-post pairings showing that overexpression of EAAT2 by chronic ceftriaxone treatment prevents the expression of STDP at corticostriatal synapses. Adapted with permission from Valtcheva and Venance (2016). *p < 0.05; **p < 0.01; ***p < 0.001.