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
Affiliations
Daniela Laricchiuta
IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Corresponding author
Juliette Gimenez
IRCCS Santa Lucia Foundation, 00143 Rome, Italy
Giuseppe Sciamanna
IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy
Andrea Termine
IRCCS Santa Lucia Foundation, 00143 Rome, Italy
Carlo Fabrizio
IRCCS Santa Lucia Foundation, 00143 Rome, Italy
Francesco Della Valle
King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, KAUST Environmental Epigenetics Program, Thuwal 23955-6900, Saudi Arabia
Silvia Caioli
Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Isernia, Italy
Luana Saba
University of Campus Biomedico, 00128 Rome, Italy
Marco De Bardi
IRCCS Santa Lucia Foundation, 00143 Rome, Italy
Francesca Balsamo
IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Human Sciences, Guglielmo Marconi University, 00166 Rome, Italy
Anna Panuccio
IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Psychology, University Sapienza of Rome, 00185 Rome, Italy
Noemi Passarello
IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Humanities, Federico II University of Naples, 80138 Naples, Italy
Anna Mattioni
IRCCS Santa Lucia Foundation, 00143 Rome, Italy
Elisa Bisicchia
IRCCS Santa Lucia Foundation, 00143 Rome, Italy
Cristina Zona
Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy
Valerio Orlando
King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, KAUST Environmental Epigenetics Program, Thuwal 23955-6900, Saudi Arabia; Corresponding author
Summary: 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.
