FIGURE 1.

Aberrant glutamate signaling contributes to E/I imbalance in AD. Increased excitation and decreased inhibition leads to an increased E/I ratio in AD as well as in other neurological diseases such as autism spectrum disorder (ASD) (Ghatak et al., 2021b). Excessive presynaptic glutamate release, disrupted glutamate re-uptake or frank release by astrocytes, and resulting increased (predominantly extrasynaptic) NMDA receptor-mediated signaling leads to increased excitation at the single neuron level, contributing to hyperexcitability in the neuronal network.