Figure 5. Aβ-induced dysfunction of inhibitory interneurons could promote aberrant synchrony in neural networks.

(a) GABAergic interneurons regulate the activity of multiple excitatory principal cells (left). Action potentials (vertical strokes) of GABAergic interneurons and excitatory principal cells generate oscillatory electrical activity that can be detected by EEG recordings (right). Aβ-induced impairments of interneurons could disrupt this regulation and elicit abnormal patterns of network activity. (b) Hypothetical diagram depicting the firing pattern of cortical pyramidal neurons (cells 1–4) in nontransgenic (left) and hAPP transgenic (right) mice. Low excitatory neuronal activity or dysfunction of inhibitory interneurons can shift the activity of excitatory neuronal populations from a normal pattern (left) to a more synchronous pattern (right). Notably, increased synchrony resulting from enhanced GABAergic activity can also lead to epileptic activity⁷⁷. (c) Actual EEG recordings from nontransgenic (left) and hAPP transgenic (right) mice. There is increased synchrony, reflected by spikes and sharp waves, in the hAPP transgenic mouse.