Absence seizures (ASs) are generalized non-convulsive seizures characterized by sudden, brief lapses in consciousness, accompanied by spike-and-wave discharges in EEG. In children with Childhood Absence Epilepsy, 30% are pharmaco-resistant and 60% exhibit neuropsychiatric deficits, that precede the epilepsy diagnosis and persist even after seizure control with medication. Thus, there is the need to fully understand and control both ASs and their comorbidities.Increased thalamic GABA levels have been observed in children with unilateral spike-and-wave discharges and drugs that elevate GABA can trigger ASs in normal individuals and worsen them in those with ASs. In animal models of ASs, strong evidence suggests a reduced GAT1-mediated GABA uptake and subsequent increase in extracellular GABA levels, leading to an increased thalamic tonic GABA-A receptor inhibition.Our study measured GAT1 function in two ASs animal models (Genetic Absence Epilepsy Rats from Strasbourg) GAERS, and Stargazer (STG) mice in the thalamus and cortex, key brain regions associated with ASs and comorbidities. We also investigated memory deficits in both models. Since Brain-Derived Neurotrophic Factor (BDNF) enhances GAT1 activity in healthy animals, we examined the effects of BDNF on ASs and memory impairments in GAERS.Our findings indicate reduced GAT1-mediated GABA uptake in both GAERS and STG compared to non-epileptic animals, whereas GAT3-mediated GABA uptake is unaffected. BDNF increases GAT1-mediated GABA uptake ex vivo, consequently reducing ASs and associated memory deficits in freely moving GAERS. This study reveals for the first time a common molecular and cellular pathway governing both ASs and their associated memory impairments.