Dopamine D2 receptors gate generalization of conditioned threat responses through mTORC1 signaling in the extended amygdala

Molecular Psychiatry
D De BundelE Valjent

Abstract

Overgeneralization of conditioned threat responses is a robust clinical marker of anxiety disorders. In overgeneralization, responses that are appropriate to threat-predicting cues are evoked by perceptually similar safety-predicting cues. Inappropriate learning of conditioned threat responses may thus form an etiological basis for anxiety disorders. The role of dopamine (DA) in memory encoding is well established. Indeed by signaling salience and valence, DA is thought to facilitate discriminative learning between stimuli representing safety or threat. However, the neuroanatomical and biochemical substrates through which DA modulates overgeneralization of threat responses remain poorly understood. Here we report that the modulation of DA D2 receptor (D2R) signaling bidirectionally regulates the consolidation of fear responses. While the blockade of D2R induces generalized threat responses, its stimulation facilitates discriminative learning between stimuli representing safety or threat. Moreover, we show that controlled threat generalization requires the coordinated activation of D2R in the bed nucleus of the stria terminalis and the central amygdala. Finally, we identify the mTORC1 cascade activation as an important molecular...Continue Reading

References

Jul 23, 1999·Annals of the New York Academy of Sciences·F A GuarraciB S Kapp
Dec 2, 1999·Experimental Cell Research·A Dufner, G Thomas
Dec 26, 2001·Brain Research. Brain Research Reviews·H W DongL W Swanson
Dec 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Emmanuel ValjentJean-Antoine Girault
May 12, 2005·Behaviour Research and Therapy·Shmuel LissekDaniel S Pine
Dec 1, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ann E WilenskyJoseph E LeDoux
Dec 15, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ryan G ParsonsFred J Helmstetter
Mar 5, 2008·Neurobiology of Learning and Memory·Jacqueline BlundellCraig M Powell
Jan 23, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jesus Bertran-GonzalezGilberto Fisone
May 22, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stephen V Mahler, Kent C Berridge
Jul 23, 2009·Science Signaling·Emanuela SantiniGilberto Fisone
Aug 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sevil DuvarciDenis Paré
Aug 21, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Michael DavisChristian Grillon
Sep 11, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jonathan P FadokRichard D Palmiter
Sep 22, 2009·Trends in Neurosciences·Emmanuel ValjentJean-Antoine Girault
Oct 20, 2010·The European Journal of Neuroscience·Jennifer C NaylorScott D Moore
Nov 12, 2010·Nature·Wulf HaubensakDavid J Anderson
Nov 12, 2010·Nature·Stephane CiocchiAndreas Lüthi
Dec 15, 2010·Neuron·Ethan S Bromberg-MartinOkihide Hikosaka
Feb 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Loredana StoicaMauro Costa-Mattioli
Jun 17, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michal KrawczykEric C Dumont
Nov 28, 2012·Cell·Zachary A KnightJeffrey M Friedman
Jan 29, 2013·Nature Neuroscience·Haohong LiBo Li
Mar 16, 2013·Science·Wei Xu, Thomas C Südhof
Mar 22, 2013·Nature·Joshua H JenningsGarret D Stuber
Sep 10, 2013·Neurobiology of Learning and Memory·Phillip E Mac CallumJacqueline Blundell
Nov 19, 2013·Nature Neuroscience·Ekaterina LikhtikJoshua A Gordon
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Mitsugu Shimobayashi, Michael N Hall
Apr 4, 2014·Nature·Seung Wook OhHongkui Zeng
Apr 11, 2014·Journal of Neurophysiology·Darrell Haufler, Denis Pare
Jul 6, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Thu N HuynhEric Klann

❮ Previous
Next ❯

Citations

Aug 18, 2017·Learning & Memory·Travis D Goode, Stephen Maren
Jan 31, 2019·Frontiers in Behavioral Neuroscience·Arun AsokJoseph B Rayman
Jun 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rongzhen YanQiang Zhou
Oct 9, 2018·Cerebral Cortex·Jivan KhlghatyanJean-Martin Beaulieu
Oct 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Bokyeong KimJa-Hyun Baik
Mar 25, 2018·Nature Communications·Anna GrossoBenedetto Sacchetti
Jun 29, 2018·Nature Neuroscience·Florian GroesslWulf Haubensak
Feb 2, 2021·Biological Psychiatry : Cognitive Neuroscience and Neuroimaging·Lauri TuominenDaphne J Holt
May 15, 2021·Behavioural Brain Research·Mi-Seon Kong, Larry S Zweifel
Aug 14, 2021·Current Biology : CB·Lizz FellingerLarry S Zweifel
Oct 13, 2021·Current Biology : CB·Claire E Stelly, Jonathan P Fadok
Dec 5, 2021·Molecular Psychiatry·Andreas FrickFredrik Åhs

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Anna K Radke
Progress in Neuro-psychopharmacology & Biological Psychiatry
Eric C Dumont
Sheng li ke xue jin zhan [Progress in physiology]
Z S Han, G Ju
Nature Reviews. Neuroscience
Darran Yates
© 2022 Meta ULC. All rights reserved