Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

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.

Journal reference: Int. J. Mol. Sci. 2021, 22, 810
DOI: 10.3390/ijms22020810

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.

Subject Areas

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

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