Synaptic and transcriptomic features of cortical and amygdala pyramidal neurons predict inefficient fear extinction.

Abstract
Fear-related disorders arise from inefficient fear extinction and have immeasurable social and economic costs. Here, we characterize mouse phenotypes that spontaneously show fear-independent behavioral traits predicting adaptive or maladaptive fear extinction. We find that, already before fear conditioning, specific morphological, electrophysiological, and transcriptomic patterns of cortical and amygdala pyramidal neurons predispose to fear-related disorders. Finally, by using an optogenetic approach, we show the possibility to rescue inefficient fear extinction by activating infralimbic pyramidal neurons and to impair fear extinction by activating prelimbic pyramidal neurons.

Citation
Laricchiuta, D., Gimenez, J., Sciamanna, G., Termine, A., Fabrizio, C., Della Valle, F., Caioli, S., Saba, L., De Bardi, M., Balsamo, F., Panuccio, A., Passarello, N., Mattioni, A., Bisicchia, E., Zona, C., Orlando, V., & Petrosini, L. (2023). Synaptic and transcriptomic features of cortical and amygdala pyramidal neurons predict inefficient fear extinction. Cell Reports, 42(9), 113066. https://doi.org/10.1016/j.celrep.2023.113066

Acknowledgements
This work was partially supported by the Italian Ministry of Health (grant number GR-2018-12365733 to D.L. and G.S.) and Ricerca Corrente Fondazione Santa Lucia (to L.P.), and by KAUST BAS 01/01 (to V.O.). Parts of the graphical abstract were created using BioRender.

Publisher
Elsevier BV

Journal
Cell reports

DOI
10.1016/j.celrep.2023.113066

PubMed ID
37656620

Additional Links
https://linkinghub.elsevier.com/retrieve/pii/S221112472301077X

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