PSD-95 in dorsal CA1 contributes to the persistence of fear memory

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.

doi:10.1101/2020.11.13.381368

bioRxiv · 10.1101/2020.11.13.381368

PSD-95 in dorsal CA1 contributes to the persistence of fear memory

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.

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Abstract

The ability to extinguish fearful memories is essential for survival. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular basis of fear memory extinction remains poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic and chemogenetic manipulations in vivo combined with PSD-95 immunostaining and 3D electron microscopy ex vivo, we demonstrate that phosphorylation of PSD-95 at serine 73 PSD-95(S73) is necessary for contextual fear extinction-induced expression of PSD-95 and synaptic plasticity. Moreover, PSD-95(S73) phosphorylation is not necessary for fear memory formation and recall but is required for extinction of contextual fear. Overall, our data shows how PSD-95-dependent synaptic plasticity in the hippocampus contributes to the persistence of fear memories.

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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.. 2020-11-15. PSD-95 in dorsal CA1 contributes to the persistence of fear memory. https://doi.org/10.1101/2020.11.13.381368

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