|Synaptic vesicles release neurotransmitters. Image credit: https://www.scientificanimations.com/
Scientists at Weill Cornell Medicine have recently solved the mystery behind why the brain cells or neurons consume energy even at rest. The mystery has puzzled them for years and now the answer to this question lies in a study published in Science Advances.
What Have Scientists Found?
In the study, scientists have recognized tiny capsules known as synaptic vesicles as a vital source of energy utilisation in inactive neurons. Synaptic vesicles are tiny, electron-lucent vesicles that are clustered at presynaptic terminals. They store neurotransmitters (the body’s chemical messengers that transmit messages between neurons) and release them by exocytosis (the process of release of substances out of the cell) in the presence of calcium. These neurotransmitters play a vital role in nerve conduction. During nerve conduction, the neurotransmitters are fired from synaptic vesicles to send a signal for communication to other neurons.
The process of packing neurotransmitters into synaptic vesicles consumes chemical energy, and scientists have discovered that this process is extremely leaky, energy-wise that it continues to uptake energy even when the vesicles are perfused and the synaptic terminals are inactive.
In previous studies, scientists saw that in inactive states like the state of coma, the consumption of glucose in the brain decreased to 50% but was still higher as compared to the uptake of glucose in other organs. This observation triggered scientists to reason behind the energy drain in the resting state.
Dr. Timothy Ryan, Professor at Weill Cornell Medicine, has shown in recent years that neuron synaptic terminals (bud-like projections at the axon terminal that fire neurotransmitters) consume more energy in their active state and are sensitive to any alterations in the fuel supply. In their new study, they inspected the fuel consumption in synaptic terminals in their inactive state. And found it higher.
They discovered the concept of high fuel consumption at the resting state for a large pool of vesicles at synaptic terminals. During the synaptic inactive state, the vesicles are filled with neurotransmitters and are ready to release them to establish communication with other neurons.
Why is Energy Used During Synaptic Inactivity?
In the study, the scientists discovered that there is a leakage of energy from vesicles in the form of protons even while they are filled up with neurotransmitters. This leakage is caused by proteins called transporters who carry the neurotransmitters into the vesicles but end up releasing the proton. By letting go of just one proton, a vesicle can gain a neurotransmitter. Evolutionarily, speculates Dr. Ryan, this makes sense, since it allows the reloading to be completed quickly during synaptic activity, which facilitates faster thinking.
According to Dr. Ryan, the study helps to understand the vulnerability of the human brain to its fuel supply. These days, the brain’s susceptibility to the disturbance in the fuel supply is a considerable issue in neurology. Also, metabolic insufficiencies have been noticed in a host of similar brain diseases including, Parkinson’s and Alzheimer’s disease. The experiment’s outcomes could help find the solutions to medical mysteries and suggest the best methods for treatment.
“If we can safely reduce the brain drain and slow the metabolism, it could be effective clinically,” Dr. Ryan concluded.