Nevertheless, PTEN is also expressed at mature synapses in the cerebral cortex and hippocampus ( Perandones et al. 2015), giving rise to a structural hyperconnectivity. This phenotype is accompanied by the appearance of abnormally large and abundant synapses ( Luikart et al.

In fact, mice with PTEN deficiency develop larger neurons, with more complex dendritic and axonal projections. Thus, some of the neurological manifestations provoked by PTEN mutation may derive from aberrant neuronal growth during brain development. PTEN is widely expressed in the central nervous system throughout development, both in neurons and glia ( Cai et al. As a negative regulator of the PI3K-PIP 3 pathway, PTEN restrains cell proliferation during embryogenesis and in adulthood ( Stiles et al. PTEN and phosphatidylinositol-3-kinase (PI3K) bidirectionally control the intracellular levels of phosphatidylinositol-(3,4,5)-triphosphate (PIP 3), an important signaling molecule that promotes cell growth and survival ( Cantley 2002). 1997), and it is now known to be a major regulator of key cellular events, including survival, proliferation, and growth ( Chow et al. Phosphatase and tensin homolog on chromosome 10 (PTEN) was originally discovered as a tumor suppressor protein ( Li et al. 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.ДЄutism, imaging, long-term depression, long-term potentiation, PI3 kinase These results suggest that synaptic actions of PTEN in the amygdala contribute to specific behavioral traits, such as sociability.

In contrast, Pten-О”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. Pten tg mice exhibit substantial microcephaly, structural hypoconnectivity, enhanced synaptic depression at cortico-amygdala synapses, reduced anxiety, and intensified social interactions. 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 (Pten tg) and knock-in of a truncated Pten gene lacking its PDZ motif (Pten-О”PDZ), which is required for interaction with synaptic proteins. In addition, it participates in synaptic plasticity processes in adulthood. 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.

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