Optogenetic stimulation of prelimbic pyramidal neurons maintains fear memories and modulates amygdala pyramidal neuron transcriptome

Daniela Laricchiuta, Giuseppe Sciamanna, Juliette Gimenez, Andrea Termine, Carlo Fabrizio, Silvia Caioli, Francesca Balsamo, Anna Panuccio, Marco De Bardi, Luana Saba, Noemi Passarello, Debora Cutuli, Anna Mattioni, Cristina Zona, Valerio Orlando, Laura Petrosini

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Article number810
Pages (from-to)1-29
Number of pages29
JournalInternational Journal of Molecular Sciences
Volume22
Issue number2
DOIs
Publication statusPublished - Jan 2 2021

Keywords

  • Differential gene expression
  • Electrophysiological recordings
  • Excitatory post-synaptic currents
  • Fear conditioning
  • Fear extinction
  • Fear-related disorders
  • Medial prefrontal cortex
  • RNA sequencing
  • Spinogenesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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