Engram reactivation mimics cellular signatures of fear

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  1. In line with this hypothesis, in natural recall there was increased316correlation between neurons and astrocytes in the shocked groups compared to the no-shock group. A317simple linear regression analysis revealed that cross-correlations had a linear relationship to average318freezing in the session. During the artificial recall session, although the Shock-ChR2 group exhibited319increased freezing levels and stereotyped calcium signatures time-locked to freezing characteristic of320natural fear, however, there were no significant differences in maximum cross-correlations. Moreover, we321observed more variability in cross-correlations between animals in both shock groups compared to322natural recall.

    This summary is really interesting, and I'd love in the discussion for you to speculate on the cellular and circuit function of correlated activity between these two populations of cells? How does this shed light on how astrocytes and neurons are affecting each other? What extracellular signals do these activity patterns make you think might be driving them?

  2. (C-D) Calcium timeseries for astrocytes (C) and neurons (D)

    Minor comment: it would be helpful to the reader to have panel titles for Astrocytes and Neurons in C and D, as well as in subsequent figures.

  3. On the other hand, neuronal calcium characteristics were not significantly different across any148groups (Figure 2L-N).

    I may be misunderstanding the panels in 2K–L, but could you explain how the Neutral measure of %dF/F in 2L is around 2, while in K it looks much lower than the shock or the eYFP peaks?

  4. jRGECO1a and GCaMP6f successfully and effectively96expressed in vHPC neurons and astrocytes, respectively (Figure 1B).

    Do you think you're getting similar expression levels (% of total cell population) of neurons and astrocytes with the calcium indicators based on histology? Do you think differences here would affect your findings?