TY - JOUR
T1 - Optogenetic stimulation of prelimbic pyramidal neurons maintains fear memories and modulates amygdala pyramidal neuron transcriptome
AU - Laricchiuta, Daniela
AU - Sciamanna, Giuseppe
AU - Gimenez, Juliette
AU - Termine, Andrea
AU - Fabrizio, Carlo
AU - Caioli, Silvia
AU - Balsamo, Francesca
AU - Panuccio, Anna
AU - De Bardi, Marco
AU - Saba, Luana
AU - Passarello, Noemi
AU - Cutuli, Debora
AU - Mattioni, Anna
AU - Zona, Cristina
AU - Orlando, Valerio
AU - Petrosini, Laura
N1 - Funding Information:
Funding: This work was supported by Italian Ministry of Health (Grant number GR-2018-12365733 to D.L. and G.S.).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/2
Y1 - 2021/1/2
N2 - 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 and amygdala gene expression to analyze the specific transcriptional pathways associated to 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 photo-activable 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 associated to 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.
AB - 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 and amygdala gene expression to analyze the specific transcriptional pathways associated to 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 photo-activable 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 associated to 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.
KW - Differential gene expression
KW - Electrophysiological recordings
KW - Excitatory post-synaptic currents
KW - Fear conditioning
KW - Fear extinction
KW - Fear-related disorders
KW - Medial prefrontal cortex
KW - RNA sequencing
KW - Spinogenesis
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U2 - 10.3390/ijms22020810
DO - 10.3390/ijms22020810
M3 - Article
AN - SCOPUS:85099578599
VL - 22
SP - 1
EP - 29
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 2
M1 - 810
ER -