Infantile neuronal ceroid lipofuscinosis (INCL) is a rare lysosomal storage disorder caused by mutations in the Cln1 gene, which encodes the Palmitoyl-Protein Thioesterase 1 (PPT1) enzyme. Like human patients, mutant mice exhibit defective autophagy, leading to widespread neuronal death accompanied by symptoms such as epilepsy, retinal and cortical degeneration, and premature death (Gupta, 2001). However, the precise mechanism linking Cln1 mutation to hyperexcitability and altered brain processing remains poorly understood. First, video-recordings in an open field arena demonstrated that CLN1 mice exhibit reduced locomotion at night (active phase) and reduced sleep. We then analysed cortical excitability under urethane anaesthesia using multi-electrode array recordings in V1. During slow-wave sleep, the spectral power of down states was raised with respect of controls, suggesting a failure of inhibition during down states, a possible hallmark of hyperexcitability. Following this result, we tested epileptic threshold by local injection of 4-aminopyridine (4-AP), a pro epileptic drug, through a protocol that does not induce seizures in controls at midday (Pracucci, 2023). Mutant mice invariably exhibited robust seizures that were blocked by superfusing the cortex with bumetanide, a NKCC1 co-transporter inhibitor, thus suggesting that hyperexcitability is associated to higher intracellular Cl levels. Our data suggest a direct link between autophagy impairment, hyperexcitability and chloride homeostasis. Further investigation of this hypothesis is crucial for a better understanding of the pathophysiology of lysosomal storage disorders.