1. Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation
- Author
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Candela Barettino, Álvaro Ballesteros-Gonzalez, Andrés Aylón, Xavier Soler-Sanchis, Leticia Ortí, Selene Díaz, Isabel Reillo, Francisco García-García, Francisco José Iborra, Cary Lai, Nathalie Dehorter, Xavier Leinekugel, Nuria Flames, Isabel Del Pino, Centro de Investigación Principe Felipe, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centro de Investigación Príncipe Felipe (CIPF), Indiana University [Bloomington], Indiana University System, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Generalitat Valenciana, Ministerio de Ciencia, Innovación y Universidades (España), European Research Council, Flames, Nuria, pellegrino, Christophe, and Flames, Nuria [0000-0003-0961-0609]
- Subjects
Serotonin ,0303 health sciences ,Neuromodulation ,QH301-705.5 ,neurodevelopmental disorders ,Neurodevelopmental disorders ,Cell Biology ,serotonin ,memory ,Cell and Developmental Biology ,03 medical and health sciences ,ErbB4 ,0302 clinical medicine ,Memory ,neuromodulation ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Biology (General) ,030217 neurology & neurosurgery ,NRG ,Original Research ,030304 developmental biology ,Developmental Biology - Abstract
17 páginas, 6 figuras, 1 tabla. Material suplementario de este artículo online en: https://www.frontiersin.org/articles/10.3389/fcell.2021.770458/full#supplementary-material, The serotonergic system of mammals innervates virtually all the central nervous system and regulates a broad spectrum of behavioral and physiological functions. In mammals, serotonergic neurons located in the rostral raphe nuclei encompass diverse sub-systems characterized by specific circuitry and functional features. Substantial evidence suggest that functional diversity of serotonergic circuits has a molecular and connectivity basis. However, the landscape of intrinsic developmental mechanisms guiding the formation of serotonergic sub-systems is unclear. Here, we employed developmental disruption of gene expression specific to serotonergic subsets to probe the contribution of the tyrosine kinase receptor ErbB4 to serotonergic circuit formation and function. Through an in vivo loss-of-function approach, we found that ErbB4 expression occurring in a subset of serotonergic neurons, is necessary for axonal arborization of defined long-range projections to the forebrain but is dispensable for the innervation of other targets of the serotonergic system. We also found that Erbb4-deletion does not change the global excitability or the number of neurons with serotonin content in the dorsal raphe nuclei. In addition, ErbB4-deficiency in serotonergic neurons leads to specific behavioral deficits in memory processing that involve aversive or social components. Altogether, our work unveils a developmental mechanism intrinsically acting through ErbB4 in subsets of serotonergic neurons to orchestrate a precise long-range circuit and ultimately involved in the formation of emotional and social memories., This work was supported by the CIDEGenT excellence research program of the Valencian government (CIDEGENT/2019/044) and by the Spanish Ministry of Science, Innovation and Universities (RTI 2018-100872-J-I00) as well as by the Young IBRO Regions Connecting Award to IDP and the ERC Consolidator Grant 101002203 to NF. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020).
- Published
- 2021