The mTOR pathway genes mTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function.

ABSTRACT: Brain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show that in utero activation of the mTORC1 activators, Rheb or mTOR, or biallelic inactivation of the mTORC1 repressors, Depdc5, Tsc1, or Pten in mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic t

SUBMITTER: Nguyen LH 

PROVIDER: S-EPMC10441381 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature