Figure 1.
A schematic of synaptic transmission at a glutamatergic tripartite synapse.
Arrival of an action potential opens voltage gated Ca2+ channels (white arrow), leading to a quick flux of calcium in the presynaptic terminal (1) that lasts between 1–2 ms. Glutamate (red circles) release in the synaptic cleft (4) takes place due to Ca2+ binding to vesicle release machinery and initiates a small inward current in the postsynaptic terminal (2) by activating the ionotropic receptors (green and orange bars). For hippocampal synapses, the probability of vesicle (5) release is small, averaging at approximately 0.2. Activation of metabotropic glutamate receptors (indigo and orange bars) on the adjacent astrocytic process (3) due to glutamate binding initiates release of Ca2+ from internal stores (6) in the astrocyte from IP3 R-mediated Ca2+ calcium channels causing an elevation in intracellular [Ca2+]. Intracellular [Ca2+]-dependent glutamate release from astrocytes triggers opening of Ca2+ stores (6) in the presynaptic terminal. Availability of two distinct sources of Ca2+ due to participation of the astrocyte increases neurotransmitter release rates. The astrocyte to neuron coupling parameter α governs the increase in presynaptic [Ca2+] and therefore the extent of potentiation.
Figure 2.
Synaptic signal transmission at a presynaptic action potential frequency of 5 Hz is shown as a function of the relative background calcium level.
The calcium is normalized to the value that maximizes synaptic transmission. The vertical line denotes the value of calcium that yields the experimentally measured transmission probability of the tripartite synapse. The inset shows the power spectrum of the postsynaptic current events at the value of calcium that maximized the signal transmission.
Figure 3.
The signal transmission in the absence of spontaneous vesicle release events and single-spike transmission probability (inset) as a function of relative background calcium level.
The vertical line (inset) denotes the value of calcium that yields the experimentally measured transmission probability of the tripartite synapse. The calcium is normalized to the value that maximizes the transmission probability.
Figure 4.
Presynaptic [Ca2+] in response to 20 Hz stimulus without (top panel) and with (center panel) feedback from the astrocyte.
Opening of the voltage gated [Ca2+] channels due to an action potential gives rise to a [Ca2+] pulse that lasts 1.25 ms in our model. The y-axes have been normalized by [Ca2+] required to generate a release probability of P≈0.2 (300 µM for the Bertram, Sherman, and Stanley model [26]). (Bottom panel) Intracellular astrocytic [Ca2+] response in the astrocyte to 20 Hz of neuronal firing.
Figure 5.
For a synapse that is functionally associated with an astrocyte, the initial neurotransmitter release triggers intracellular Ca2+ elevation and a consequential glutamate release from the astrocyte.
Due to the positive feedback from the astrocyte, the dynamical increase in release probability (total DP≈3) until it saturates at P≈5 is shown. When the feedback from the astrocyte is absent the release probability fluctuates around P≈0.2 (see inset).
Figure 6.
Synaptic transmission (not normalized here, but at a fixed presynaptic spiking frequency of 5 Hz) versus astrocytic feedback.
The baseline transmission probability is fixed P≈0.18, while the number of active zones varies. The vertical line denotes the value of α that yields the experimentally measured transmission probability of the tripartite synapse.
Figure 7.
Transmission of information as a function of feedback from the astrocyte under the assumption that the synapse we used for calibration has one active zone for vesicle release.
The vertical line denotes the value of the feedback strength (α = 0.101 ms−1) that yields the experimentally measured transmission probability of the tripartite synapse.
Figure 8.
The information transmission (not normalized here, but at a fixed presynaptic spiking frequency of 5 Hz) is shown as a function of the astrocytic feedback at various baseline synaptic transmission probabilities P and a fixed number (2) of active zones.
The vertical line denotes the value of α which corresponds to the experimental tripartite synapse.
Table 1.
Rate constants for the release model by Bertram, Sherman, and Stanley [26].
Table 2.
Parameters for asynchronous release (Equation 1).
Table 3.
Parameters for Tsodyks and Markram model (Equations 2 and 3).
Table 4.
Parameters IP3 production mediated by neuronal firing (Equation 5).
Table 5.
Parameters of the modified Li-Rinzel model for astrocytic Ca2+ oscillations (Equations 6–9).
Table 6.
Parameters for presynaptic calcium (Equation 10).