Alzheimer's disease (AD) is the most common form of dementia after the age of 65. Prior to cognitive impairment, this disease is characterized by a long asymptomatic phase during which dysfunctions of neurotransmission have been demonstrated. It is known that these early dysfunctions are the result of an abnormal accumulation of β-amyloid peptide which accumulates in different regions of the brain, notably the hippocampus. By performing electrophysiological recordings on the APP/PS1 transgenic mouse model that show an overproduction of β-amyloid peptide, I identified an alteration of the inhibitory transmission in the hippocampus of these mice at 1 month. This dysfunction appears to originate from a loss of chlorine homeostasis in hippocampal neurons. In most neurons, the transmembrane Cl- gradient is mainly regulated by KCC2 cotransporters that maintain intracellular Cl- concentration at relatively low levels. After quantification of total KCC2 expression using biochemical techniques, I demonstrated a decrease in their expression in APP/PS1 mice. Interestingly, after treatment with CLP 257, a compound that can improve KCC2 function and expression, I restored the inhibitory neurotransmission, thus confirming the critical role of KCC2 in the early dysfunctions observed in APP/PS1 mice. In view of these last results, an in vivo study is necessary to establish if a preventive treatment with CLP can contribute to correct the defects of the inhibitory transmission not only at an early but also at a late stage of AD. This study will reveal whether CLP can be considered as a new treatments targeting the early stages of AD.