Activity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance

Figure 4

Short- and long-term plasticity of astroglial glutamate uptake. (a) Simultaneous recordings of neuronal responses (fEPSPs; field excitatory postsynaptic potentials) and astroglial glutamate transporter currents (STCs) revealed paired-pulse facilitation of both fEPSPs and astroglial glutamate uptake in hippocampal CA1 region. Sample traces are shown for fEPSPs (top) and astroglial STCs (bottom). STCs were recorded in the presence of 5 mM kynurenic acid. Scale bars = 0.25 mV for fEPSP, 50 pA for astroglial currents, 25 ms. (b-c) Patch-clamp recordings revealed short-term facilitation of astroglial extrasynaptic currents (ESCs) in the cerebellum. Sample traces are shown for ESCs in response to 10 pulses of (b) 10 Hz or (c) 100 Hz stimulation to parallel fibers. (d-e) Astroglial GLT-1 glutamate transporter is responsible for glutamate uptake during late but not early phase of long-term potentiation (LTP) in the hippocampus. (d) Bar graphs showing that the GLT-1 inhibitor, dihydrokainate (DHK), inhibited glutamate uptake during late phase (L-LTP; right panel), but not early phase (E-LTP; left panel) of LTP induced by high frequency stimulation of SCs (HFS; each composed of two trains of 100 Hz pulses separated by 20 s). Glutamate uptake in hippocampal slices were measured using radioactive glutamate (L-[14C(U)]-glutamic acid). (e) Western blot analysis revealed a significant upregulation of neuronal glutamate transporter (EAAC1) expression during E-LTP (left panel) and of GLT-1 during L-LTP (right panel). Representative western blots are shown above bar graphs. (f) Recordings of fEPSPs in hippocampal CA1 region showed that an increase in GLT-1 activity and glutamate uptake are required for the induction of additional LTP. LTP was triggered twice in the same experiment (LTP-1 and LTP-2). Each LTP was induced by HFS as indicated by arrows (HFS-1 and HFS-2). During LTP-1, no difference was observed between slices treated with DHK (open triangles) and control (filled circles) indicating that basal GLT-1 activity was not required for induction of LTP-1. After the establishment of a new baseline, an additional LTP (LTP-2) was triggered under control conditions (filled circles). This was completely inhibited in slices treated with DHK (open circles). The effect of DHK was abolished in the presence of a glutamate scavenger (glutamic-pyruvic transaminase + pyruvate). These suggested that an increase in GLT-1 activity above basal level and the accompanying enhanced glutamate uptake is important for the induction of LTP-2. Mean ± SEM are shown for (d–f). Adapted with permission: (a) [12], (b-c) [10], (d-e) [19], and (f) [20].