Optogenetic Stimulation of Prelimbic Pyramidal Neurons Maintains Fear Memories and Modulates Amygdala Pyramidal Neuron Transcriptome.
Amygdala
/ cytology
Animals
Conditioning, Classical
/ physiology
Electrophysiological Phenomena
Excitatory Postsynaptic Potentials
/ physiology
Extinction, Psychological
/ physiology
Fear
/ physiology
Male
Memory
/ physiology
Mice, Transgenic
Neural Pathways
/ cytology
Optogenetics
/ methods
Prefrontal Cortex
/ cytology
Pyramidal Cells
/ metabolism
Synaptic Transmission
/ physiology
Transcriptome
/ genetics
RNA sequencing
differential gene expression
electrophysiological recordings
excitatory post-synaptic currents
fear conditioning
fear extinction
fear-related disorders
medial prefrontal cortex
spinogenesis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 Jan 2021
15 Jan 2021
Historique:
received:
04
12
2020
revised:
12
01
2021
accepted:
12
01
2021
entrez:
20
1
2021
pubmed:
21
1
2021
medline:
13
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33467450
pii: ijms22020810
doi: 10.3390/ijms22020810
pmc: PMC7830910
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero della Salute
ID : GR-2018-12365733
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