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Neuron ; 103(1): 133-146.e8, 2019 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-31104950

RESUMEN

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.


Asunto(s)
Miedo/fisiología , Hipotálamo/fisiología , Memoria/fisiología , Oxitocina/fisiología , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/fisiología , Animales , Ambiente , Extinción Psicológica/fisiología , Miedo/psicología , Femenino , Reacción Cataléptica de Congelación , Silenciador del Gen , Ácido Glutámico/metabolismo , Hipotálamo/citología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Optogenética , Oxitocina/genética , Ratas , Ratas Wistar
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