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A fear memory engram and its plasticity in the hypothalamic oxytocin system

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Hasan,  Mazahir T.
Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society;
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Mazahir Hasan Group, Max Planck Institute for Medical Research, Max Planck Society;

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Althammer,  Ferdinand
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Eliava,  Marina
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Valery Grinevich Group, Max Planck Institute for Medical Research, Max Planck Society;

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Raftogianni,  Androniki
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Knobloch,  Sophie
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Jain,  Apar
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Dogbevia,  Godwin
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Mazahir Hasan Group, Max Planck Institute for Medical Research, Max Planck Society;
Rolf Sprengel Group, Max Planck Institute for Medical Research, Max Planck Society;

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Bertocchi,  Ilaria
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Rolf Sprengel Group, Max Planck Institute for Medical Research, Max Planck Society;

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Larkum,  Matthew E.
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;
Cortical Circuits, Max Planck Institute for Medical Research, Max Planck Society;

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Sprengel,  Rolf
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Rolf Sprengel Group, Max Planck Institute for Medical Research, Max Planck Society;
Olfaction Web, Max Planck Institute for Medical Research, Max Planck Society;

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Grinevich,  Valery
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Valery Grinevich Group, Max Planck Institute for Medical Research, Max Planck Society;

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Citation

Hasan, M. T., Althammer, F., da Gouveia, M. S., Goyon, S., Eliava, M., Lefevre, A., et al. (2019). A fear memory engram and its plasticity in the hypothalamic oxytocin system. Neuron. doi:10.1016/j.neuron.2019.04.029.


Cite as: http://hdl.handle.net/21.11116/0000-0003-A0EC-E
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.