A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System.
Amygdala
/ metabolism
Animals
Environment
Extinction, Psychological
/ physiology
Fear
/ physiology
Female
Freezing Reaction, Cataleptic
Gene Silencing
Glutamic Acid
/ metabolism
Hypothalamus
/ cytology
Memory
/ physiology
Neuronal Plasticity
/ physiology
Neurons
/ physiology
Optogenetics
Oxytocin
/ genetics
Rats
Rats, Wistar
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
03 07 2019
03 07 2019
Historique:
received:
18
05
2018
revised:
08
10
2018
accepted:
18
04
2019
pubmed:
21
5
2019
medline:
23
10
2019
entrez:
21
5
2019
Statut:
ppublish
Résumé
Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram.
Identifiants
pubmed: 31104950
pii: S0896-6273(19)30386-1
doi: 10.1016/j.neuron.2019.04.029
pii:
doi:
Substances chimiques
Glutamic Acid
3KX376GY7L
Oxytocin
50-56-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
133-146.e8Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.