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Disrupting Reconsolidation of Fear Memory in Humans by a Noradrenergic β-Blocker
Published on: December 18, 2014
A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System
Mazahir T Hasan1, Ferdinand Althammer2, Miriam Silva da Gouveia2
1Laboratory of Memory Circuits, Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Sede Building, Barrio Sarriena, 48940 Leioa, Spain; Ikerbasque-Basque Foundation for Science, 48013 Bilbao, Spain; Neurocure, Charité-Universitätsmedizin, Virchowweg 6, 10117 Berlin, Germany; Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
Abstract:
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.
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