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Although hyperactivation of mTOR has been strongly linked to the development of epilepsy and, conversely, inhibition of mTOR by rapamycin treatment is protective against seizures in several models, the downstream epileptic mechanisms have remained elusive. Autophagy, a catabolic process that plays a vital role in cellular homeostasis by mediating the turnover of cytoplasmic constituents, is negatively regulated by mTOR. Here we demonstrate that autophagy is suppressed in brain tissues of forebrain-specific conditional TSC1 and phosphatase and tensin homlog knock-out mice, both of which display aberrant mTOR activation and seizures. In addition, we also discovered that autophagy is suppressed in the brains of human TSC patients. Moreover, conditional deletion of<jats:italic>Atg7<\/jats:italic>, an essential regulator of autophagy, in mouse forebrain neurons is sufficient to promote development of spontaneous seizures. Thus, our study suggests that impaired autophagy contributes to epileptogenesis, which may be of interest as a potential therapeutic target for epilepsy treatment and\/or prevention.<\/jats:p>","DOI":"10.1523\/jneurosci.2392-12.2012","type":"journal-article","created":{"date-parts":[[2012,11,7]],"date-time":"2012-11-07T17:38:02Z","timestamp":1352309882000},"page":"15704-15714","source":"Crossref","is-referenced-by-count":133,"title":["Impaired Autophagy in Neurons after Disinhibition of Mammalian Target of Rapamycin and Its Contribution to 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