PTEN Activity Defines an Axis for Plasticity at Cortico-Amygdala Synapses and Influences Social Behavior

Cristina Sánchez-Puelles, Mariá Calleja-Felipe, Alberto Ouro, Ghassen Bougamra, Ana Arroyo, Ibai Diez, Asier Erramuzpe, Jesús Cortés, José Martínez-Hernández, Rafael Luján, Marta Navarrete, César Venero, Andrew Chan, Miguel Morales, José A. Esteban, Shira Knafo

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)505-524
Number of pages20
JournalCerebral Cortex
Issue number2
StatePublished - 21 Mar 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved.


  • autism
  • imaging
  • long-term depression
  • long-term potentiation
  • PI3 kinase
  • Amygdala/physiology
  • Hippocampus/physiology
  • PTEN Phosphohydrolase/physiology
  • Synapses/physiology
  • Male
  • Mice, Transgenic
  • Animals
  • Neuronal Plasticity
  • Social Behavior
  • Memory/physiology
  • Cerebral Cortex/physiology
  • Female

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience


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