PTEN Activity Defines an Axis for Plasticity at Cortico-Amygdala Synapses and Influences Social Behavior
Por:
Sánchez-Puelles C., Calleja-Felipe M., Ouro A., Bougamra G., Arroyo A., Diez I., Erramuzpe A., Cortés J., Martínez-Hernández J., Luján R., Navarrete M., Venero C., Chan A., Morales M., Esteban J.A., Knafo S.
Publicada:
1 ene 2020
Resumen:
Phosphatase and tensin homolog on chromosome 10 (PTEN) is a tumor suppressor and autism-associated gene that exerts an important influence over neuronal structure and function during development. In addition, it participates in synaptic plasticity processes in adulthood. As an attempt to assess synaptic and developmental mechanisms by which PTEN can modulate cognitive function, we studied the consequences of 2 different genetic manipulations in mice: presence of additional genomic copies of the Pten gene (Ptentg) and knock-in of a truncated Pten gene lacking its PDZ motif (Pten-?PDZ), which is required for interaction with synaptic proteins. Ptentg mice exhibit substantial microcephaly, structural hypoconnectivity, enhanced synaptic depression at cortico-amygdala synapses, reduced anxiety, and intensified social interactions. In contrast, Pten-?PDZ mice have a much more restricted phenotype, with normal synaptic connectivity, but impaired synaptic depression at cortico-amygdala synapses and virtually abolished social interactions. These results suggest that synaptic actions of PTEN in the amygdala contribute to specific behavioral traits, such as sociability. Also, PTEN appears to function as a bidirectional rheostat in the amygdala: reduction in PTEN activity at synapses is associated with less sociability, whereas enhanced PTEN activity accompanies hypersocial behavior. © 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved.
Filiaciones:
Molecular Cognition Laboratory, Biophysics Institute, Consejo Superior de Investigaciones Cientificas (CSIC), University of the Basque Country (UPV), Euskal Herriko University (EHU), Campus Universidad Del País Vasco, Leioa, 48940, Spain
Department of Molecular Neurobiology, Centro de Biologiá Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Madrid, 28049, Spain
Computational Neuroimaging Laboratory, Biocruces Health Research Institute, Barakaldo, 48903, Spain
Ikerbasque, Basque Foundation for Science, Bilbao, 48013, Spain
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, 48940, Spain
Department of Psychobiology, Universidad Nacional de Educación A Distancia, Madrid, 28040, Spain
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong
Department of Physiology and Cell Biology, National Institute of Biotechnology in the Negev, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel
|