Any comments on this work are greatly appreciated, let’s make science participative!!! 14/14

Finally, science wouldn’t be fun without friends, so big shoutout to everyone in the lab (veterelab.weebly.com) who either participated directly in the project, or helped by being the best of friends,Flora, Nadja, Pablo, Nina, Livia, and so many others... 13/14

There’s quite a bit of additional stuff and neat observations, but that’s the gist of it! Once again, very proud of this project, conducted with my amazing mentor @gisellavetere.bsky.social ! I couldn’t have hoped for a better team to do my PhD in. 12/14

2) FC cells are mostly reactivated in similar quantity and quality; and 3) that “shock” and “freezing” populations differ in their coordinated reactivation at recall, which parallels some observations we saw in opto experiments. 11/14

We then used calcium imaging to study how the populations we opto-tagged actually behaved during encoding and recall of a fear memory, and showed that 1) the four populations we designated are very distinct from one another; 10/14

We indeed showed that, in both these cases, opto reactivation didn’t trigger recall, proving that our past results really targeted engram-encoding populations of the dCA1. 9/14

Specifically, we tagged “shock”-active cells during immediate shock, and “freezing”-active cells during sweeping; two paradigms in which animals do not form an associative memory with the context. 8/14

I remember the excitement after analyzing the first batches of animals and realizing this was the case! We quickly decided to control if this effect could be explained by any non-memory related tagging: 7/14

We found that only reactivation of “shock” or ”freezing” active cells could trigger memory recall. In other words, it seems that engram encoding consists in a selection process, sensitive to internal/external correlates of activity!! (I suspect this to be rather dCA1-specific). 6/14

Combined with a DLC-based closed-loop opto setup, we were able to tag (and subsequently manipulate) dCA1 neurons active during “pre-shock”, “shock”, “freezing”, and “no-freezing” in different animals. 5/14

Instead, we made use of f-FLiCRE, an even faster variant of FLiCRE from the great Tina Kim (and produced for us by @brimble.bsky.social), allowing us to selectively manipulate the activity of cells active at different FC moments (some only a few secs long, which we also tested in-vitro). 4/14

However, technical limitations have limited progress into determining the identity of these so-called “engram cells”. Specifically, drug/IEG techs indifferently tags neurons active in a >1h time window, which only allows the manipulation of FC-active cells as a whole. 3/14

Tons of amazing papers have revealed how reactivating neurons active during memory acquisition (specifically, FC) can trigger memory recall. These built the foundation of engram research as we know it today. 2/14

Our preprint of my PhD’s work in @gisellavetere.bsky.social lab is finally out on BiorXiv: doi.org/10.1101/2024..., and I’m so excited to share it! If you’ve ever wondered about reconciling engram manipulation experiments and neuronal activity during encoding, you’re on the right thread! 1/14

Amazing work, and thanks for the thread! I'll definitely use this as my next journal club