AMP-activated protein kinase is essential for the maintenance of energy levels during synaptic activation

While accounting for 2% of the total body mass, the brain is the organ that consumes the most energy. Although it is widely acknowledged that neuronal energy metabolism is tightly regulated, the mechanism how neurons meet their energy demand to sustain synaptic transmission remains poorly studied. Here we provide substantial evidence that the AMP-activated protein kinase (AMPK) plays a leading role in this process. Our results show that following synaptic activation, AMPK activation is required to sustain neuronal energy levels particularly through mitochondrial respiration. Further, our studies revealed that this metabolic plasticity regulated by AMPK is required for the expression of immediate early genes, synaptic plasticity and memory formation. These findings are important in the context of neurodegenerative disorders, as AMPK deregulation as it is observed in Alzheimer’s disease, impairs the metabolic response to synaptic activation. Altogether, our data provides the proof of concept that AMPK is an essential player in the regulation of neuroenergetic metabolism plasticity induced in response to synaptic activation.