Inhibitory input directs astrocyte morphogenesis through glial GABABR
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Abstract
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Excitatory neurons exhibited decreased sEPSC activity via cell average and K-S test, while exhibiting no significant difference in sIPSC activities in cell averages and a significant difference via K-S test (Fig. 3e-f). Analysis of inhibitory neurons revealed increased sEPSC amplitudes and decreased sIPSC amplitudes via K-S test, which were not statistically significant when averaged across cells (Fig. 3g-h).
My reading of this is that excitatory neuronal activity in these circuits decreases when astrocytic Gabbr1 is knocked out of astrocytes, but inhibitory activity seems to be less affected. Do you think this points to a homeostatic mechanism by which astrocytes may help regulate excitatory/inhibitory balance in developing cortical circuits? It would be interesting to see if this sort of effect would also occur in adult animals, …
Excitatory neurons exhibited decreased sEPSC activity via cell average and K-S test, while exhibiting no significant difference in sIPSC activities in cell averages and a significant difference via K-S test (Fig. 3e-f). Analysis of inhibitory neurons revealed increased sEPSC amplitudes and decreased sIPSC amplitudes via K-S test, which were not statistically significant when averaged across cells (Fig. 3g-h).
My reading of this is that excitatory neuronal activity in these circuits decreases when astrocytic Gabbr1 is knocked out of astrocytes, but inhibitory activity seems to be less affected. Do you think this points to a homeostatic mechanism by which astrocytes may help regulate excitatory/inhibitory balance in developing cortical circuits? It would be interesting to see if this sort of effect would also occur in adult animals, after circuit maturation. Another interesting follow-up may be to think about how much this sort of homeostatic mechanism is driven by physiology or morphology of the astrocytes.
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Gabbr1 regulates Ednrb1 during astrocyte morphogenesis
It's very exciting that you found a mechanism downstream of Gabbr1 that has known cytoskeletal function. Maybe I missed this, but do you have an idea about how activation of Gabbr1 might lead to Ednrb upregulation? (Or why Gabbr1 KO leads to down-regulation?)
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we found no changes in spontaneous Ca2+ activity in cortical astrocytes from the Gabbr1-cKO
Did you observe any changes in intracellular calcium besides frequency or delta F? In some of our experiments, we find that most salient changes in calcium are related to the propagation or area of the calcium signal. The negative result in calcium here implies that the spontaneous calcium activity in developing cortical astrocytes does not arise from spontaneous inhibitory (GABAergic) signal, which is interesting in light of previous studies. Do you think there might be a developmental timecourse over which astrocytes become responsive to spontaneous release of GABA?
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Together, these observations indicate that input from inhibitory neurons contributes to astrocyte morphogenesis in the developing cortex.
Exciting stuff! In this experiment, since the manipulation is neuronal, it's very cool that you see astrocyte-specific morphological effects. I wonder if there also may be neuronal morphology changes at the subcellular level that could precede or accompany the astrocytic changes.
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