Reduced GABAA, slow synaptic inhibition in Alzheimer's disease
M Bruce MacIver1, Robert A Pearce2
1Stanford University School of Medicine, Stanford, CA, USA.
None:
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-GABAA, slow synaptic current-was studied using whole-cell recordings in hippocampal brain slices from AD model mice (tg-APPSwe). The investigators found that GABAA, 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.
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