Understanding epileptogenesis in molecular terms may provide clues as to how to intervene pharmacologically to prevent or cure this disorder.Here,we reported that kindling,an animal model of limbic epilepsy,increased the expression of NRSF (Neuronal repressor element-1 silencing transcription factor),a Küppel-type zinc-finger transcription factor and a potent silencer of neuron-specific genes in non-neuronal cells.To understand the functional significance of NRSF in kindling,we conditionally knocked out NRSF in the forebrain of adult mice using the Cre-loxP system.We found that the development of kindling was dramatically accelerated in the knockout mice.The downstream NRSF target genes,including BDNF,GluR2,Na1.2,were up-regulated in the knockout mice after seizure activity.Furthermore,knockout NRSF abolished the anti-epileptogenic effects of the glycolytic inhibitor 2-deoxy-D-glucose.Our results revealed that NRSF plays a critical role in limbic epileptogenesis and is the molecular target of "ketogenic diet" (low in carbohydrates and high in fat),an altemative therapy for drug-resistant epilepsy.