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

Daniela Laricchiuta; Juliette Gimenez; Giuseppe Sciamanna; Andrea Termine; Carlo Fabrizio; Francesco Della Valle; Silvia Caioli; Luana Saba; Marco De Bardi; Francesca Balsamo; Anna Panuccio; Noemi Passarello; Anna Mattioni; Elisa Bisicchia; Cristina Zona; Valerio Orlando; Laura Petrosini

doi:10.1016/j.celrep.2023.113066

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

Cell Rep. 2023 Sep 26;42(9):113066. doi: 10.1016/j.celrep.2023.113066. Epub 2023 Aug 31.

Authors

Daniela Laricchiuta¹, Juliette Gimenez², Giuseppe Sciamanna³, Andrea Termine², Carlo Fabrizio², Francesco Della Valle⁴, Silvia Caioli⁵, Luana Saba⁶, Marco De Bardi², Francesca Balsamo⁷, Anna Panuccio⁸, Noemi Passarello⁹, Anna Mattioni², Elisa Bisicchia², Cristina Zona¹⁰, Valerio Orlando¹¹, Laura Petrosini²

Affiliations

¹ IRCCS Santa Lucia Foundation, 00143 Rome, Italy. Electronic address: daniela.laricchiuta@unipg.it.
² IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
³ IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy.
⁴ King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, KAUST Environmental Epigenetics Program, Thuwal 23955-6900, Saudi Arabia.
⁵ Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Isernia, Italy.
⁶ University of Campus Biomedico, 00128 Rome, Italy.
⁷ IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Human Sciences, Guglielmo Marconi University, 00166 Rome, Italy.
⁸ IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Psychology, University Sapienza of Rome, 00185 Rome, Italy.
⁹ IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Humanities, Federico II University of Naples, 80138 Naples, Italy.
¹⁰ Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy.
¹¹ King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, KAUST Environmental Epigenetics Program, Thuwal 23955-6900, Saudi Arabia. Electronic address: Valerio.Orlando@kaust.edu.sa.

PMID: 37656620
DOI: 10.1016/j.celrep.2023.113066

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.

Keywords: CP: Cell biology; CP: Neuroscience; amygdala; cellular excitability; dendritic spines; infralimbic cortex; medial prefrontal cortex; optogenetic stimulations; post-traumatic stress disorders; prelimbic cortex; transcriptome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amygdala / physiology
Animals
Extinction, Psychological / physiology
Fear* / physiology
Mice
Prefrontal Cortex* / physiology
Pyramidal Cells / physiology
Transcriptome / genetics