A Tale of Two Stories: Astrocyte Regulation of Synaptic Depression and Facilitation

Abstract

Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity. While a consensus has emerged that the resulting decrease (depression) and/or increase (facilitation) of the synapse strength are crucial to neuronal computations, their modes of expression in vivo remain unclear. Recent experimental studies have reported that glial cells, particularly astrocytes in the hippocampus, are able to modulate short-term plasticity but the mechanism of such a modulation is poorly understood. 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 counterintuitive effects. Depending on the expressed presynaptic signaling pathways, astrocytes may globally inhibit or potentiate the synapse: the amount of released neurotransmitter in the presence of the astrocyte is transiently smaller or larger than in its absence. But this global effect usually coexists with the opposite local effect on 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 Ca2+ oscillations controls the effects of the astrocyte on short-term synaptic plasticity. Our model explains several experimental observations yet unsolved, and uncovers astrocytic gliotransmission as a possible transient switch between short-term paired-pulse depression and facilitation. This possibility has deep implications on the processing of neuronal spikes and resulting information transfer at synapses.

Regulation of rhythm genesis by volume-limited, astroglia-like signals in neural networks

“…(In this study, we did not consider a theoretically plausible feedback effect associating neuronal firing frequency with astroglial actions [48]. ) Second, to mimic the action of volume-limited astroglia, we constrained the above inhibitory action to the clusters of neighbouring BCs which contained the same numbers of individual cells, for comparison.…”

Variations in myo-inositol in fronto-limbic regions and clinical response to electroconvulsive therapy in major depression

“…An internal increase in glial calcium can also spur neuronal activity through the action of astrocyte secreted transmitters. These glia released transmitters have been shown to partake in critical neuronal activities such as long term (Perea et al, 2009) and short-term (De Pittà et al, 2011) synaptic plasticity as well as other critical synaptic changes (Volterra, 2014, Halassa and Haydon, 2010). …”

Degeneracy in hippocampal physiology and plasticity

“…Specifically, several of the components involved in the induction and expression of long-term plasticity have also been shown to play critical roles in short-term forms of plasticity such as paired pulse facilitation, and on the synaptic filters that they mediate (Atwood et al, 2014;Bouchard et al, 2003;De Pitta et al, 2011;Dittman et al, 2000;Emptage et al, 2001;Fioravante and Regehr, 2011;Fortune and Rose, 2001;Regehr, 2012;Siegelbaum, 2000;Zucker, 1989Zucker, , 1999Zucker and Regehr, 2002). …”