Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.13.381368v1?rss=1 Authors: Ziolkowska, M., Borczyk, M., Nowacka, A., Nalberczak-Skora, M., Sliwinska, M. A., Robaca, M., Lukasiewicz, K., Caly, A., Skonieczna, E., Tomaszewski, K. F., Wojtowicz, T., Wlodarczyk, J., Bernas, T., Salamian, A., Radwanska, K. Abstract: The ability to update and extinguish fearful memories is essential for survival. 30 Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. 31 However, the cellular and molecular basis of fear memory updating remains poorly 32 understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of 33 glutamatergic synapses. Here, we investigated the role of dCA1 PSD-95-driven synaptic 34 plasticity in contextual fear extinction. Using dCA1-targeted genetic manipulations in vivo 35 combined with PSD-95 immunostaining and 3D electron microscopy ex vivo, we demonstrate 36 that phosphorylation of PSD-95 at serine 73 PSD-95(S73) is necessary for contextual fear 37 extinction-induced expression of PSD-95 and remodeling of glutamatergic synapses. 38 Surprisingly, PSD-95 phosphorylation is not necessary for fear memory formation or early 39 extinction but is required for updating a partly extinguished fear memory, affecting its 40 persistence. Using a chemogenetic manipulation, we confirm that updating of the partly 41 extinguished fear requires PSD-95 expression and dCA1 activity during a prior extinction 42 session. Overall, our data indicate that dCA1 synapses are remodeled upon the extinction of 43 contextual fear memories; this process relies on PSD-95(S73) phosphorylation and enables 44 future updating of a partly extinguished contextual fear memory. These findings show how 45 the hippocampus may contribute to the persistence of fear memories. Copy rights belong to original authors. Visit the link for more info