Big congrats!!!

Not this fos one but both monoclonal rat (226017) & rabbit (226008) one and I am happy. Also every SySy AB I used was always great (on flow, in ICC, IHC, WB). Totally worth its money

Thanks a lot!! :-)

@davidvcbrito.bsky.social happy to share this honour with you!

Many thanks to all the (bluesky-less) collaborators and institutions @zi-mannheim.bsky.social @uniheidelberg.bsky.social who have made this possible.

Special thanks to my great former supervisor Ana & colleague David!

Lastly, we wanted to see what the mechanism behind this is. Given the fact that Npas4 is known to be important for excitation-inhibition balance, we teamed up with electrophysiologists and found that Npas4 second wave increased CCK-specific inhibitory input in CA1.

Blocking Npas4 second wave resulted in less context discrimination (and vice versa) and the fear memory was unable to be extinguished.
Thus, Npas4 second wave suppresses maladaptive fear processes.

The fear conditioning paradigm we used is a highly salient training that can cause PTDS-like phenotypes.
This led us to speculate whether this second wave of Npas4 expression is crucial to avoid maladaptive associations and to allow cognitive flexibility.

Thereby, we showed that the second wave has a different effect on memory consolidation than the first Npas4 peak 🤯

Quite surprising and puzzling 🤔🤔🤔

But Npas4 is known to be a positive memory regulator, how does our data fit into this?

On the other hand, inducing the second wave in the weak protocol decreased fear expression.

Given Npas4’s property to be Ca2+ &NMDAR dependent, we saw that 2nd wave can be blocked by inhibiting NMDAR signaling using APV infusion.

How does this second wave affect memory consolidation?
Blocking the expression of the second wave by inhibiting NMDAR signaling increased the fear memory.

We showed very strong (3x0.7mA shock) fear training results in a biphasic Npas4 expression in CA1: the classical IEGs peak at 15min, and another at 4h after CFC. The second wave is missing in a weak CFC (1x0.2mA shock).
Strong fear = second wave 🌊🌊
weak fear = no second wave 🌊

Love it - such a nice idea! And totally agree that accepted animal applications should be recognised more! :D

@danai-lama.bsky.social I totally agree! Amazing talk and data and @alicia-walker.bsky.social was just great, enthusiastic and cheerful in her presentation.
#engramsandensembles2025 is delivering :-)

Congrats!! Very nice study