Astrocyte regulation of presynaptic plasticity

Background / Purpose:

Short-term presynaptic plasticity designates changes of synaptic strength whereby the amount of released neurotransmitter upon presynaptic stimulation varies over seconds, depending on neuronal firing. While a consensus has emerged that such decreases (depression) and/or increases (facilitation) of synaptic gain are crucial to neuronal computations, their modes of expression in vivo remain unclear.

Recent experimental studies have reported that astrocytes, the main type of glial cells in the hippocampus and in the cortex, are able to modulate short-term plasticity, yet the mechanism of such a modulation is poorly understood.

Main conclusion:

Here, we investigate the characteristics of short-term plasticity modulation by astrocytes using a biophysically realistic computational model. Mean-field analysis of the model, supported by intensive numerical simulations, unravels that astrocytes may mediate counter-intuitive effects. Depending on the expressed presynaptic signaling pathways, astrocytes may globally decrease or increase synaptic release: that is, the amount of released neurotransmitter in the presence of the astrocyte is transiently smaller or larger than in its absence. However, this global effect usually coexists with the opposite local effect on input paired pulses: with release-decreasing astrocytes, most paired pulses become facilitated, namely the amount of neurotransmitter released upon spike i+1 is larger than that at spike i, while paired-pulse depression becomes prominent under release-increasing astrocytes. Moreover, we show that the frequency of astrocytic intracellular Ca ²⁺ oscillations controls the effects of the astrocyte on short-term synaptic plasticity.

Next steps:

Our model explains several experimental observations yet unsolved, and unravels gliotransmission from the astrocyte as a possible transient switch between short-term paired-pulse depression and facilitation. This possibility has strong implications for the processing of neuronal spikes and resulting information transfer at synapses.

Disclosures:
No relevant competing interests disclosed.

Grants:
U.S. National Science Foundation I2CAM International Materials Institute Award, DMR-0844115 and DMR-0645461
National Science Foundation (NSF), PHY 0216576 and 0225630
Tauber Family Fundation, Tauber Fund to Tel Aviv University