Behavioral analyses in rodent models of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is typically associated with epilepsy, but patients also present with a myriad of comorbid neuropsychiatric disorders. TSC is caused by mutations in the tuberous sclerosis complex genes 1 or 2 (TSC1, TSC2). This TSC1/2 complex serves as a negative regulator of the mammalian target of rapamycin (mTOR) signaling pathway, which plays a crucial role in regulating neuronal function, including cell proliferation, survival, growth, and protein synthesis. Mutations result in hyperactivation of the pathway. Animal models with mutations in Tsc1 or Tsc2 consistently exhibit epilepsy and behavioral phenotypes. Additionally, abnormal neuronal populations can impact the broader network, leading to deficits in learning and memory, anxiety-like behaviors, deficits in social behaviors, and perseverative and repetitive behaviors. This review aims to synthesize the existing animal literature linking TSC models to epileptogenesis and behavioral impairments, with insights on how modifications in TSC signaling influence both the structure and function of neurons and behavior. Understanding these relationships may provide valuable insights into potential therapeutic targets for managing epilepsy and neuropsychiatric disorders associated with TSC dysregulation.