Figure 4.

Glutamate or ATP released from astrocytes regulates transitions between facilitation and depression of synaptic transmission. (A) Conceptual framework for the regulation of synaptic release probability at basal conditions by astrocytes. Astrocyte-released glutamate increases basal synaptic release probability (U₀), whereas astrocyte-released ATP/Adn generally decreases it. (B) Changes in synaptic release probability due to astrocytic gliotransmitters can be detected by variations of paired-pulse plasticity quantified by paired-pulse ratio (PPR). Paired-pulse facilitation (left, green traces) of postsynaptic currents (PSCs) corresponds to PPR values above 1 (right, green-shaded area) whereas paired-pulse depression (left, magenta traces) are associated with PPR values below 1 (right, magenta-shaded area). (C) Raster plots of simulated PSC pairs for 100 different input spike trains with same statistics colored according to the paired-pulse ratio: green for facilitation, PPR > 1; magenta for depression, PPR < 1. For increasing rates of exocytosis of gliotransmitter from the astrocyte, mimicked by increasing rates of Ca²⁺ crossing beyond the threshold for exocytosis (top row, red dashed line), synaptic plasticity could be progressively changed to its opposite depending on the type of gliotransmitter. Astrocytic glutamate could thus turn facilitating synapses into depressing (middle row) whereas astrocyte-derived ATP or adenosine could turn depressing synapses into facilitating (bottom row). Simulations are based on a model of astrocyte-regulation of synaptic release introduced in De Pittà et al. (2011). “Basal Synaptic Release Probability” in (B) refers to the probability of synaptic release at rest, that is when synaptic activity is assumed to be very low and the amount of neurotransmitter released upon arrival of an action potential to the presynaptic terminal is essentially independent of previous release events (Zucker and Regehr, 2002; De Pittà et al., 2011).