FIGURE 1.

Schematic of impaired long term potentiation (LTP) due to lack of AQP4. In WT mice, AQP4 facilitates the bidirectional transport of water and is seen colocalized with GLT-1 and Kir4.1. Extracellular glutamate and potassium is taken up by GLT-1 and Kir4.1, respectively. Binding of glutamate to NMDA receptor (NMDAR) and AMPA receptors (AMPAR) increases calcium influx and promotes surface expression of AMPAR (not shown). The influx of calcium also modulates brain-derived neurotrophic factor (BDNF). Binding of BDNF to TrkB is regulated through three pathways: PLCγ, PI3K, and MAPK which activates the transcription factor CREB that further promotes gene expression to induce LTP. In AQP4-null animals potassium reuptake in astrocytes is impaired. NMDAR is also dysregulated which may result in loss of calcium influx and ultimately lack of BDNF-TrkB binding which inhibits CREB activation and downstream effects important to synaptic plasticity.