, 29 May 2019
A Fear Memory Engram and its Plasticity in the Hypothalamic Oxytocin System
>> Free access until August 22 clicking on this link
Hasan MT 1 , Althammer F 2 , Silva da Gouveia M 2 , Goyon S 3 , Eliava M 2 , Lefevre A 2 , Kerspern D 3 , Schimmer J 2 , Raftogianni A 2 , Wahis J 3 , Knobloch-Bollmann HS 2 , Tang Y 2 , Liu X 2 , Jain A 2 , Chavant V 3 , Goumon Y 3 , Weislogel JM 4 , Hurlemann R 5 , Herpertz SC 6 , Pitzer C 7 , Darbon P 3 , Dogbevia GK 8 , Bertocchi I 9 , Larkum ME 10 , Sprengel R 9 , Bading H 4 , Charlet A 11 , Grinevich V 12
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.
B) The vast majority of OT neurons (99.4% ± 0.8%, green) of the PVN and SON were labeled via a constitutive OT promoter driving hChR2-mCherry (B1, red).
B2) Fear expression induced tagging (ChR2-mCherry, red) of a small population of OT neurons (green). (B1 and B2) Vertical panels depict ChR2-mCherry-containing axons (red) with OT-immunopositive puncta (green, appearing in yellow) in the CeL of both groups.
1 Laboratory 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. Electronic address: email@example.com.
2 Schaller Research Group on Neuropeptides, German Cancer Research Center, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
3 Centre National de la Recherche Scientifique and University of Strasbourg, Institute of Cellular and Integrative Neurosciences, 8 Allée du Général Rouvillois, 67000 Strasbourg, France.
4 Department of Neurobiology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
5 Department of Psychiatry and Division of Medical Psychology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
6 Department of General Psychiatry, Center of Psychosocial Medicine, Heidelberg University, Voßstraße 4, 69115 Heidelberg, Germany.
7 Interdisciplinary Neurobehavioral Core (INBC), Heidelberg University, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.
8 Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
9 University of Torino, Department of Neuroscience Rita Levi Montalcini and Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, 10043, Torino, Italy.
10 Neurocure, Charité-Universitätsmedizin, Virchowweg 6, 10117 Berlin, Germany.
11 Centre National de la Recherche Scientifique and University of Strasbourg, Institute of Cellular and Integrative Neurosciences, 8 Allée du Général Rouvillois, 67000 Strasbourg, France; University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France. Electronic address: firstname.lastname@example.org.
12 Schaller Research Group on Neuropeptides, German Cancer Research Center, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany; Department of Neuropeptide Research for Psychiatry, Central Institute of Mental Health, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: email@example.com.
Events & Meetings
The main goal of the BraYn initiative is to organize a scientific conference involving different laboratories across Italy and Europe where young researchers, especially PhD students and junior postdocs, can share their knowledge, skills and ideas to establish new collaborations between different research groups.