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.

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 🌊

Honoured to be awarded
Young Investigator Neuroscience Award from CHS Foundation together with my dearest David Brito for our paper in Molecular Psychiatry!

Curios about the work
⬇️⬇️⬇️ check out our paper & my 🧵 below
www.nature.com/articles/s41...

Check out our latest review on

Molecular and cellular mechanisms that support recent and remote memory

We highlight:
• structural and functional changes at the engram level

• hippocampal-cortical communication required for systems consolidation

doi.org/10.1016/j.nl...

Finally in its nice looking journal style 🤩🥳🍾

Check out our paper about DNA methylation, engram maturation and systems consolidation.

You can find a 🧵 on my previous link
bsky.app/profile/jani...

Thanks to all people involved and the journal for awarding it "Priority Communication"