PTEN Activity Defines an Axis for Plasticity at Cortico-Amygdala Synapses and Influences Social Behavior
| Autor: | Sánchez-Puelles, Cristina, Calleja-Felipe, M., Ouro, Alberto, Bougamra G, Arroyo, A., Diez, I., Erramuzpe, A., Cortés, J., Martínez-Hernández, José, Luján, Rafael, Navarrete, Marta, Venero, César, Chan, A., Morales, M., Esteban, J.A., Knafo, Shira |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Ministerio de Sanidad (España), Universidad del País Vasco, Junta de Comunidades de Castilla-La Mancha |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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-ΔPDZ), 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-ΔPDZ 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. Spanish Ministry of Economy and Competitiveness (SAF2016-78071-R and SAF2015-62540-ERC to S.K.; PCIN-2016-095 and SAF2017-86983-R to J.A.E.; BFU201563769-R to R.L.; SAF2014-58598-JIN and RYC-2016-20414 to M.N.); Basque Ministry of Health (RIS3 and ELKARTEK to S.K.); University of the BasqueCountry (EHUrOPE14/03 to S.K.); Junta de Comunidades de Castilla–La Mancha (PPII2014-005-P to R.L.); Spanish Ministry of Economy and Competitiveness (BES-2011-043464 to C.S.-P.). |
| Databáze: | OpenAIRE |
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