Montalban, EnricaAl-Massadi Iglesias, OmarSancho Balsells, AnnaBrito, VerónicaPins, Benoit deAlberch, JordiGinés, SilviaGirault, Jean-AntoineGiralt, Albert2020-05-282020-05-282019Montalban, E., Al-Massadi, O., Sancho-Balsells, A., Brito, V., Pins, B. d., Alberch, J., Ginés, S., Girault, J.A. and Giralt,A. (2019). Pyk2 in the amygdala modulates chronic stress sequelae via PSD-95-related micro-structural changes. Transl. Psychiatry 9, 3. doi: 10.1038/s41398-018-0352-y2158-3188http://hdl.handle.net/10347/22630Major depressive disorder (MDD) is a common disorder with a variety of symptoms including mood alterations, anhedonia, sleep and appetite disorders, and cognitive disturbances. Stressful life events are among the strongest risk factors for developing MDD. At the cellular level, chronic stress results in the modification of dendritic spine morphology and density. Here, we study the role of Pyk2 in the development of depressive-like symptoms induced by a model of chronic unpredictable mild stress (CUMS). Pyk2 is a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the forebrain principal neurons and involved in spine structure and density regulation. We show that Pyk2 knockout mice are less affected to anxiety-like and anhedonia-like phenotypes induced by the CUMS paradigm. Using region-specific knockout, we demonstrate that this phenotype is fully recapitulated by selective Pyk2 inactivation in the amygdala. We also show that in the absence of Pyk2 the spine alterations, PSD-95 clustering, and NMDA receptors changes induced by the CUMS paradigm are prevented. Our results reveal a possible role for Pyk2 in the response to stress and in synaptic markers expression and spine density regulation in the amygdala. We suggest that Pyk2 contributes to stress-induced responses through micro-structural changes and that its deficit may contribute to the resilience to chronic stresseng© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/Pyk2 proteinAmygdalaStressMiceMajor depressive disorderjournal article10.1038/s41398-018-0352-yopen access