Reduced GABA A, slow synaptic inhibition in Alzheimer's disease

Altered synaptic physiology clearly contributes to memory loss and other CNS symptoms in Alzheimer's disease. A new paper in this issue of the Journal of Alzheimer's Disease, from Zhe Jin's group in Uppsala, Sweden, adds important new information to help us understand how. A powerful, yet largely uncharacterized form of neuronal inhibition—GABA A, slow synaptic current—was studied using whole-cell recordings in hippocampal brain slices from AD model mice (tg-APPSwe). The investigators found that GABA A, slow inhibition was significantly reduced in dentate granule neurons from aged AD mice, compared to both wild type and adult non-aged AD mice. This reduction would nicely explain the change in excitatory-inhibitory balance previously reported in this and other AD model animals, as well as impairments in pattern separation and theta-gamma cross-frequency coupling that are early manifestations of AD.