Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Unforgettable: Optogenetic Stimulation of Prelimbic Pyramidal Neurons Maintains Fear Memories by Modulating Amygdala Pyramidal Neuron Transcriptome

Daniela Laricchiuta
* ORCID logo ,
Giuseppe Sciamanna
,
Juliette Gimenez
ORCID logo ,
Andrea Termine
ORCID logo ,
Carlo Fabrizio
ORCID logo ,
Silvia Caioli
,
Francesca Balsamo
,
Anna Panuccio
,
Marco De Bardi
,
Luana Saba
,
Noemi Passarello
,
Debora Cutuli
,
Anna Mattioni
,
Cristina Zona
,
Valerio Orlando
,
Laura Petrosini
Version 1 : Received: 4 December 2020 / Approved: 10 December 2020 / Online: 10 December 2020 (11:38:50 CET)

A peer-reviewed article of this Preprint also exists.

Laricchiuta, D.; Sciamanna, G.; Gimenez, J.; Termine, A.; Fabrizio, C.; Caioli, S.; Balsamo, F.; Panuccio, A.; De Bardi, M.; Saba, L.; Passarello, N.; Cutuli, D.; Mattioni, A.; Zona, C.; Orlando, V.; Petrosini, L. Optogenetic Stimulation of Prelimbic Pyramidal Neurons Maintains Fear Memories and Modulates Amygdala Pyramidal Neuron Transcriptome. Int. J. Mol. Sci. 2021, 22, 810. Laricchiuta, D.; Sciamanna, G.; Gimenez, J.; Termine, A.; Fabrizio, C.; Caioli, S.; Balsamo, F.; Panuccio, A.; De Bardi, M.; Saba, L.; Passarello, N.; Cutuli, D.; Mattioni, A.; Zona, C.; Orlando, V.; Petrosini, L. Optogenetic Stimulation of Prelimbic Pyramidal Neurons Maintains Fear Memories and Modulates Amygdala Pyramidal Neuron Transcriptome. Int. J. Mol. Sci. 2021, 22, 810.

Abstract

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and in strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

Keywords

Fear extinction; Fear Conditioning; Medial Prefrontal Cortex; RNA sequencing; Differential Gene Expression; Electrophysiological Recordings; Excitatory Post-Synaptic Currents; Spinogenesis; Fear-related Disorders

Subject

Social Sciences, Psychology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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