Neural circuits of anxiety
Anxiety disorders include nine classes of psychiatric diseases and represent the most prevalent psychiatric conditions with an estimated prevalence of 18% among adults, and more than 28% over a lifetime. Despite the high personal and societal costs of anxiety disorders, relatively few therapeutic targets have been identified and current threatments are limited and have side effects. The main reason for these limitation is that we still do not understand the neural substrate underlying these pathologies. A leading hypothesis posits that anxiety disorders are caused by dysfunctions of neural circuits encoding emotional valence. Brain regions encoding emotional valence have been identified in humans and animal models, but the functional role of the circuits including these regions are just starting to be identified.
The insular cortex, or insula, is a brain region responding to emotional stimulation in healthy individuals, and has been shown to be overactivated in patients with different types of anxiety disorders such as generalized anxiety disorder, social anxiety disorder or specific phobia. However, very few is known regarding the anatomo-functional organization of this brain region, and the circuits involving the insula.
Our research program aims at defining the circuit, cellular and synaptic organization of the insular cortex in healthy conditions using mice models, and to determine whether alterations of this organization is causally linked to pathological level of anxiety. The long term goal of our research is to restore the neural dysfunctions underlying anxiety disorders in pre-clinical models to translate our findings to develop novel strategies to treat anxiety disorders.
Mots clés
Apprentissage, Bio-senseurs, Comportement, Connectivité, Emotion, Imagerie cellulaire in vitro ou in vivo, Motivation, Mémoire, Optogénétique, Optogénétique et chemogénétique, Stress, Toxicomanie, Troubles addictifsSelected publications
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How an anxious heart talks to the brain
Yoni Couderc, Anna Beyeler.
Nature. 2023-03-01. 615 (7951) : 217-218.
DOI: 10.1038/d41586-023-00502-6 -
Neurotensin orchestrates valence assignment in the amygdala
Hao Li, Praneeth Namburi, Jacob M. Olson, Matilde Borio, Mackenzie E. Lemieux, Anna Beyeler, Gwendolyn G. Calhoon, Natsuko Hitora-Imamura, Austin A. Coley, Avraham Libster, Aneesh Bal, Xin Jin, Huan Wang, Caroline Jia, Sourav R. Choudhury, Xi Shi, Ada C. Felix-Ortiz, Verónica de la Fuente, Vanessa P. Barth, Hunter O. King, Ehsan M. Izadmehr, Jasmin S. Revanna, Kanha Batra, Kyle B. Fischer, Laurel R. Keyes, Nancy Padilla-Coreano, Cody A. Siciliano, Kenneth M. McCullough, Romy Wichmann, Kerry J. Ressler, Ila R. Fiete, Feng Zhang, Yulong Li, Kay M. Tye.
Nature. 2022-07-20.
DOI: 10.1038/s41586-022-04964-y -
Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration
Roman Serrat, Ana Covelo, Vladimir Kouskoff, Sebastien Delcasso, Andrea Ruiz-Calvo, Nicolas Chenouard, Carol Stella, Corinne Blancard, Benedicte Salin, Francisca Julio-Kalajzić, Astrid Cannich, Federico Massa, Marjorie Varilh, Severine Deforges, Laurie M. Robin, Diego De Stefani, Arnau Busquets-Garcia, Frederic Gambino, Anna Beyeler, Sandrine Pouvreau, Giovanni Marsicano.
Cell Reports. 2021-12-01. 37 (12) : 110133.
DOI: 10.1016/j.celrep.2021.110133 -
Linking emotional valence and anxiety in a mouse insula-amygdala circuit
Céline Nicolas, Anes Ju, Yifan Wu, Hazim Eldirdiri, Sebastien Delcasso, Débora Jacky, Laura Supiot, Claudia Fornari, Adrien Vérité, Maxime Masson, Silvia Rodriguez-Rozada, J. Simon Wiegert, Anna Beyeler.
PrePrint ResearchSquare. 2021-10-26.
DOI: 10.21203/rs.3.rs-964107/v1 -
A new player in neural circuits of emotions
Anes Ju, Anna Beyeler.
Nat Neurosci. 2021-10-15.
DOI: 10.1038/s41593-021-00945-y -
Probing the polarity of spontaneous perisomatic GABAergic synaptic transmission in the mouse CA3 circuit in vivo.
Olivier Dubanet, Arnaldo Ferreira Gomes Da Silva, Andreas Frick, Hajime Hirase, Anna Beyeler, Xavier Leinekugel.
Cell Reports. 2021-07-01. 36 (2) : 109381.
DOI: 10.1016/j.celrep.2021.109381 -
Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex
Anes Ju, Beatriz Fernandez-Arroyo, Yifan Wu, Débora Jacky, Anna Beyeler.
Mol Brain. 2020-06-29. 13 (1)
DOI: 10.1186/s13041-020-00605-5 -
Neurobiological links between stress and anxiety
Nuria Daviu, Michael R. Bruchas, Bita Moghaddam, Carmen Sandi, Anna Beyeler.
Neurobiology of Stress. 2019-11-01. 11 : 100191.
DOI: 10.1016/j.ynstr.2019.100191 -
Valence coding in amygdala circuits
Michele Pignatelli, Anna Beyeler.
Current Opinion in Behavioral Sciences. 2015-04-01. 26 : 97-106.
DOI: 10.1016/j.cobeha.2018.10.010 -
Organization of Valence-Encoding and Projection-Defined Neurons in the Basolateral Amygdala
Anna Beyeler, Chia-Jung Chang, Margaux Silvestre, Clémentine Lévêque, Praneeth Namburi, Craig P. Wildes, Kay M. Tye.
Cell Reports. 2018-01-23. 22 (4) : 905-918.
DOI: 10.1016/j.celrep.2017.12.097 -
Parsing reward from aversion
A. Beyeler.
Science. 2016-11-03. 354 (6312) : 558-558.
DOI: 10.1126/science.aak9762 -
Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval
Anna Beyeler, Praneeth Namburi, Gordon F. Glober, Clémence Simonnet, Gwendolyn G. Calhoon, Garrett F. Conyers, Robert Luck, Craig P. Wildes, Kay M. Tye.
Neuron. 2016-04-01. 90 (2) : 348-361.
DOI: 10.1016/j.neuron.2016.03.004 -
A circuit mechanism for differentiating positive and negative associations
Praneeth Namburi, Anna Beyeler, Suzuko Yorozu, Gwendolyn G. Calhoon, Sarah A. Halbert, Romy Wichmann, Stephanie S. Holden, Kim L. Mertens, Melodi Anahtar, Ada C. Felix-Ortiz, Ian R. Wickersham, Jesse M. Gray, Kay M. Tye.
Nature. 2015-04-01. 520 (7549) : 675-678.
DOI: 10.1038/nature14366