Genetic rescue of Pten-KO induced hypoexcitability and signaling changes in cortical neurons.
Cullen, Erin R
Cullen, Erin R
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Abstract
Pten is a negative regulator of the mTORC1 and mTORC2 complexes, and its deletion is well known to induce epilepsy. The effects of Pten deletion on neuronal membrane properties, synaptic transmission, and cell signaling have been studied extensively in the hippocampus, but have not previously been measured in the developed cortex, even though Pten mutation in humans is associated with cortical dysplasia. We induced a Pten deletion in excitatory and inhibitory neurons in the mouse neocortex using a Cre-lox system and recorded neuron properties with whole cell patch clamp between 20 and 30 days later. Changes in membrane properties of Pten KO neurons were similar to those previously observed in hippocampal neurons, and inhibition of mTORC1 and mTORC2 rescued these changes, possibly to different extents. Pten KO neurons also showed a marginally significant increase in the number of spontaneous excitatory synaptic events compared to controls, and this property was rescued by neither mTORC1 nor mTORC2 inhibition. We conclude that Pten has similar effects on membrane properties in the cortex and hippocampus, and that mTORC1 and mTORC2 might both be involved in generating the changes induced by Pten mutation.
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Graduate
Date
2021-01-01