Synaptic Vesicles Found Responsible for Significant Brain Energy Consumption

In a new study published today in Science Advances, researchers from Weill Cornell Medicine have identified synaptic vesicles as a major source of energy consumption in inactive neurons.

“These findings help us understand better why the human brain is so vulnerable to the interruption or weakening of its fuel supply,” said senior author Timothy Ryan. Ryan and his team have shown in recent years that neurons’ synaptic terminals are major consumers of energy when active, and are very sensitive to any disruption of their fuel supply. In the new study, they examined fuel use in synaptic terminals when inactive, and found that it is still high.

This high resting fuel consumption, they discovered, is accounted for largely by the pool of vesicles at synaptic terminals. During synaptic inactivity, vesicles are fully loaded with thousands of neurotransmitters each and are ready to launch these signal-carrying payloads across synapses to partner neurons. researchers discovered that there is a leakage of energy from the vesicle membrane, a proton efflux, such that a proton pump enzyme in the vesicle has to keep working, and consuming fuel as it does so, even when the vesicle is already full of neurotransmitter molecules.

The experiments pointed to transporters as the likely sources of this proton leakage. Transporters normally bring neurotransmitters into vesicles, changing shape to carry the neurotransmitter in, but allowing at the same time for a proton to escape—as they do so. Dr. Ryan speculates that the energy threshold for this transporter shape-shift was set low by evolution to enable faster neurotransmitter reloading during synaptic activity, and thus faster thinking and action.