Thursday, January 27, 2022

Why do neurons consume so much energy even when at rest?

Brain Drain: The finding is a significant advance in understanding the basic biology of the brain.

Like all the other parts of your body, your brain needs the energy to operate. The brain consumes about 20 percent of the body’s energy. It remains a fuel-guzzler even when its neurons are not firing signals called neurotransmitters to each other.

A new study at Weill Cornell Medicine explains why the brain needs so much energy. Scientists found that packaging neurotransmitters are probably responsible for this energy drain.

The human brain generally has a very small safety factor with respect to fuel supply. For example, when blood glucose levels drop, severe neurological consequences ensue. This study demonstrates why the human brain is so vulnerable to the interruption or weakening of its fuel supply.

Scientists identified that tiny capsules called synaptic vesicles in inactive neurons are a significant source of energy drain. These vesicles, used by neurons, act as containers for their neurotransmitter molecules. The communication ports called synaptic terminals fire these molecules to signal to other neurons.

Packing neurotransmitters into vesicles is a process that consumes chemical energy. Scientists found this process, energy-wise is inherently leaky. It is so leaky that it consistently devours energy even when the vesicles are filled and synaptic terminals are inactive.

Scientists have found that neurons’ synaptic terminals are significant energy drainers in recent years. They are very active and sensitive to any disruption of their fuel supply. In this study, scientists studied fuel use in synaptic terminals when they are inactive. Interestingly, they found that the energy consumption is still high.

Scientists noted, “This high resting fuel consumption 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.”

Why would a synaptic vesicle consume energy even when fully loaded?

This happens due to energy leakage from the vesicle membrane, a “proton efflux.” A special “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 likely suggest that the protein transporters are the primary source of proton leakage. These transporters bring neurotransmitters into vesicles. This changes the vesicles’ shape to carry the neurotransmitter while allowing the proton to escape at the same time.

Scientists observed 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.

Dr. Timothy Ryan, a professor of biochemistry and biochemistry in anesthesiology at Weill Cornell Medicine, said“The downside of a faster loading capability would be that even random thermal fluctuations could trigger the transporter shape-shift, causing this continual energy drain even when no neurotransmitter is being loaded.”

“Although the leakage per vesicle would be tiny, there are at least hundreds of trillions of synaptic vesicles in the human brain so that the energy drain would add up.”

Journal Reference:

  1. Camila Pulido, Timothy A. Ryan. Synaptic vesicle pools are a major hidden resting metabolic burden of nerve terminals. Science Advances, 2021; 7 (49) DOI: 10.1126/sciadv.abi9027

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