How the brain powers communication between neurons



The roughly 86 billion neurons in the human brain are wired together into intricate communication networks connected by cell-to-cell junctures called synapses. Sending signals over these networks and across synapses requires a lot of energy, which is produced by cellular structures called mitochondria in the form of a chemical called ATP. Neurons are very long, narrow structures, so most of their synapses are not located near mitochondria. However, how cells send mitochondria to active synapses to supply them with energy is not well understood.


IRP researchers led by Zu-Hang Sheng, Ph.D., investigated how synapses get the energy they need to power the intense communication thought to underlie learning and memory formation. They found that local levels of ATP drop during this type of synaptic activity. This drop triggers a series of chemical reactions controlled by an energy sensor called AMP-activated protein kinase (AMPK) that ultimately leads to the rapid recruitment of mitochondria to synapses in order to restore the local energy supply. Genetically blocking or chemically interfering with this energy feedback loop prevented the delivery of mitochondria to synapses and depleted energy levels there, which reduced synaptic responses during intense neuronal communication.


These findings revealed an energy feedback loop that plays a critical role in providing the energy needed to sustain synaptic communication throughout the nervous system. This new understanding may lead to insights into — and possible interventions for — a range of neurological disorders and age-related neurodegenerative diseases that are associated with impaired transport of mitochondria, insufficient cellular energy supplies, and problems with sending signals across synapses.


Li S, Xiong GJ, Huang N, Sheng ZH. (2020). The crosstalk of energy sensing and mitochondrial anchoring sustains synaptic efficacy by maintaining presynaptic metabolism. Nat. Metab. Oct. 5;2:1077-1095.