FIGURE 4.

Circuit‐specific astrocytic control of LTP onto medial perforant path fibers via activation of presynaptic GluN3A‐NMDA receptors. Schematic illustration of our data showing that astrocytic signaling onto GluN3A‐containing pre‐NMDA receptors controls the dynamic range for LTP at MPP‐GC synapses by modulating the probability of glutamate release (Pr). Left panel: In the presence of intact astrocyte signaling, high‐frequency stimulation (HFS) of MPP fibers induces LTP and conveys spatial information cues to the DG. Right panel: When the astrocyte control is abolished by either genetic deletion of the GluN3A subunit (Agarwal et al., 2017) or by infusing BAPTA into the astrocyte (Akers et al., 2014), LTP magnitude is increased following HFS of MPP fibers, revealing the role of the astrocyte cascade. Based on these data, we propose (graphs in the lower part of the panels) that the astrocyte control sets the basal strength of MPP‐GC synapses to a significant level of pre‐potentiation, which leaves a range for further potentiation by HFS stimulation (left), that is smaller than the one seen when the astrocyte control on basal release probability is abolished by the above manipulations (right). Excerpt from Savtchouk et al., ²⁰¹⁹. The authors hold the copyright under the CC BY‐NC‐ND license to reproduce figures from Savtchouk et al., PNAS 2019, https://creativecommons.org/licenses/by‐nc‐nd/4.0/ for the summary of terms and conditions