Mechanisms of synapse regulation via astrocytes

[Pythagorean]

theoretical modeling approach

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.

PLoS Computational Biology article “A Tale of Two Stories: Astrocyte Regulation of Synaptic Depression and Facilitation” by Maurizio De Pittà, Vladislav Volman, Hugues Berry & Eshel Ben-Jacob

 

[Moonbear]

The role of glia in synaptic plasticity gets revisited every so often as if it's totally new. There's literature dating back at least 20 years on the topic. I dabbled in this area of research years ago, but ran into technical difficulties that hindered progress and I ended up just dropping it when I couldn't find a way around those problems. I keep hoping every time a manuscript crosses my desk that someone has found a way to get further. Do you have a more complete citation for this so I can look up the article? I'm still interested in the topic, even if not actively pursuing it any more.

 

[Pythagorean]

It's always a question to me when I model a neural network, "what determines the neuron's properties". I just set them constant based on experimental and/or theoretical considerations. The computational neurogenetics approach puts a genetic network within each neuron so that some underlying network produces the neuron's electrophysiological properties (as a function of time and/or 'environment' now instead of constant), but astrocytes have an interesting electrophysiological relationship with neurons already through gap junctions, now we have another important member of the network, rather than as a sub-network.

I wonder how many studies that use gap junction openers/closers are ignorantly affecting neuro-glial interactions (rather than neuro-neuro reactions that are generally reported).

Here's the doi and such:

De Pittà M, Volman V, Berry H, Ben-Jacob E (2011) A Tale of Two Stories: Astrocyte Regulation of Synaptic Depression and Facilitation. PLoS Comput Biol 7(12): e1002293. doi:10.1371/journal.pcbi.1002293