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I’m delighted to be able to share with you all what I’ve been doing during my postdoc - this work was published today “stress gates an astrocytic energy reservoir to impair synaptic plasticity” https://www.nature.com/articles/s41467-020-15778-9
A thread of what we found
A thread of what we found
I should probably start by adding a disclaimer for the diehard @stressynomics fans - this paper contains no CRH, no hypothalamus, not even a mention of PVN 
Stress has very distinct effects on synaptic function. These hallmarks can even be used to quantify stress, eg. short-term plasticity used to measure social transmission and buffering of stress - Sterley et al. 2018 http://doi.org/10.1038/s41593-017-0044-6
In this paper we set out to tackle the question of how stress impairs long-term plasticity, as stress induces a robust synaptic phenotype in this form of plasticity too - MacDougall & Howland 2013 http://doi.org/10.1093/cercor/bhs247
Of course, being an ‘astrocyte person’, I approached this question thinking that astrocyte dysfunction could be responsible for impaired LTP following stress as astrocyte function is critical for the expression of LTP eg. Henneberger et al. 2010 http://doi.org/10.1038/nature08673
When we put more thought into this hypothesis it made sense to implicate astrocytes in the effects of stress on synaptic function. First, there is abundant literature showing astrocytic changes in human stress-related disorders
Nagy et al. 2017 http://doi.org/10.1093/ijnp/pyw071
Nagy et al. 2017 http://doi.org/10.1093/ijnp/pyw071
Second, astrocytes express abundant glucocorticoid receptors. Even more than neurons according to http://brainrnaseq.org
Also, astrocytes line the cerebrovasculature giving them presumed first access to stress hormones which enter the brain through the blood.
Also, astrocytes line the cerebrovasculature giving them presumed first access to stress hormones which enter the brain through the blood.
In our paper we show that acute stress changes astrocyte gene expression, morphology, calcium signalling, and expression of gap junction channel proteins.
We measured functional gap junction coupling between astrocytes in real time using patch clamp and 2P microscopy to show that movement of fluorescent dye and glucose between astrocytes was impaired by stress (see below for experiment).
One consequence of decreased network function of astrocytes was impaired L-lactate release in response to synaptic stimulation*
*actually initial release was fine (supplementary), sustained release over the course of a typical LTP experiment was impaired (below)
*actually initial release was fine (supplementary), sustained release over the course of a typical LTP experiment was impaired (below)
Finally, we showed that supplying a stressed astrocyte, which has been effectively cut off from its network, with L-lactate was sufficient to rescue the effects of stress on LTP at nearby synapses!
These data suggest that stress induced modification of astrocyte network function limits energy availability at the synapse. This in turn results in the failure of LTP expression, which was the case both in somatosensory cortex and hippocampus.
This work builds upon a lot of past research, and links stress with rapid (90 minutes after stress) alterations in astrocyte structure and function with downstream consequences on neuronal transmission.
Finally, I want to add that I am starting my own lab @CRCHUM in @UMontreal this year and I am looking to recruit people interested in pursuing this kind of research. Reach out by DM or email if you are interested. More here - http://murphyroyallab.org
