Phosphatase and tensin homologue (PTEN) regulates synaptic plasticity independently of its effect on neuronal morphology and migration

Non‐technical summary  The sizes of neurons and their synaptic connections are regulated by multiple molecular mechanisms to provide neuronal networks that perform well‐defined functions. Deletion of the tumour suppressor phosphatase and tensin homologue (PTEN) during early development leads to a 2‐ to 3‐fold increase in neuronal and synaptic size and abnormalities in synaptic plasticity, the cellular mechanism underlying learning and memory. Whether PTEN deletion affects synaptic plasticity directly or as a consequence of its effect on the neuronal and synaptic size remained unclear. Here we show that deletion of the Pten gene Pten in mice during postnatal development, when the central nervous system is formed, does not affect neuronal or synaptic size but impairs synaptic plasticity. Thus, PTEN affects neuronal structure and synaptic plasticity through independent mechanisms.