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. 2021 Feb 22;10:e63819. doi: 10.7554/eLife.63819

Figure 7. EAATs regulate synaptic integration by UBCs.

Figure 7.

(A) Example of AMPAR-mediated EPSC in 1 mM TEA. Top: Single EPSC size (all-or-nothing) at the first stimulation intensity that evoked a current (black). Two stimulation intensities below threshold (light and dark gray) had no EPSC response. Bottom: The same trace with a longer timebase showing the all-or-nothing slow EPSC that occurred at the same stimulation intensity as the fast EPSC. (B) Top: Application of DL-TBOA to the same cell as in (A) reveals slow EPSCs at stimulation intensities below the level that evoked the fast EPSC (red). Note the reduction in EPSC amplitude due to tonic desensitization. Bottom: In DL-TBOA, the slow EPSCs are much longer than in TEA alone. Without DL-TBOA, only 1 of 11 cells had multiple EPSC levels. In DL-TBOA, five of seven cells had at least two different EPSC sizes, indicating that EAATs prevent AMPARs from detecting multiple mossy fibers during strong synaptic stimulation. (C) Top: Fast EPSC amplitudes (relative to the maximal fast EPSC under the same bath conditions) plotted as a function of synaptic stimulation intensity (relative to the lowest intensity that evoked the fast EPSC under the same bath conditions). Both before and after DL-TBOA, the fast EPSC is all-or-nothing. Bottom: Same as above, but showing slow EPSCs. In DL-TBOA, there are multiple amplitude levels. The slow EPSC amplitudes are relative to the maximal slow EPSC in the same bath conditions and the x-axis is relative to the lowest stimulation intensity that evoked the maximal slow EPSC. Error bars mean and SEM. Pink and gray lines are individual experiments. (D) Interpretation of these results. In control conditions (left) glutamate is released from the mossy fiber (MF), detected by the receptors on the UBC, then removed from the synaptic cleft by astrocytes (A). When glutamate transporters are inhibited, not only does ambient glutamate build up (blue background), but glutamate released from neighboring synapses is sensed and integrated as slow rising and slow decaying synaptic currents. Thus, glutamate transporters prevent cross-talk between glomeruli and therefore underlie the ability of glomeruli to function as discrete processing units.