The human brain has a prodigious appetite; although it makes up just 2 percent of the body’s mass, it consumes a full 20 percent of its energy. Scientists had long believed this was partly due to wasteful flaws in how nerve cells transmit electrical signals. But a new study suggests that this process is actually ultra-efficient, a finding that could alter not just our basic understanding of the brain’s energy budget and evolution but how we interpret brain scans.
To explain how the brain uses energy, scientists and textbook writers had drawn largely from the pioneering work of Alan Lloyd Hodgkin and Andrew Huxley, whose detailed model of the action potential—or nerve impulse—in squid giant nerve cells earned them a Nobel prize in 1963. The team discovered that these nerve signals used about four times as much energy as the theoretical minimum. In other words, the squid cells were about 25 percent efficient—about the same level of effectiveness as a modern car combustion engine.
This energy loss comes about because nerve impulses have two opposing—but overlapping—phases. To generate and keep a nerve impulse going, neurons open sodium channels, allowing sodium ions to rush into the cell and generate a positive current. Potassium gates open a little later, creating a current in the opposite direction to bring the cell back to near its original voltage. The longer both gates are open simultaneously, the greater the wasted energy.
In the new work, instead of studying oversized squid neurons, Henrik Alle of the Max Planck Institute for Brain Research, in Frankfurt, Germany, and his colleagues looked at rat neurons. They used a patch clamp technique, a relatively new method that allows them to measure electrical signals from just a tiny portion of a cell.
“Teaching from time to time educates,” Alle says. “In late spring of 2008, I prepared a tutorial for first-year medical students. I wondered whether I really should tell students that axonal action potentials are as inefficient as could be read from [textbooks]: inward and outward currents overlapping to such a large extent that the efficiency was only 25 percent. Would nature really do something like this?”
Alle’s suspicions were spot-on. He and his team report in the Sept. 11 issue of Science that in rats the potassium gates open later than was previously thought. Thus, signal transmission took only about 1.3 times as much energy as that required by a perfect capacitor; that is, these cells were three times more efficient than the squid neurons.
“What this paper in Science shows is that nerve cells are actually very thrifty; the overlap in currents is minimal,” says Pierre Magistretti, a professor at the Brain Mind Institute at the Ecole Polytechnique Fédérale de Lausanne in Switzerland who wrote an accompanying perspective piece in Science. “The cells have to bring in less sodium, and therefore activate less the sodium-potassium pump. It means you have to use less energy.”
Reinterpreting brain scans
The new findings offer an answer to longstanding questions about how the brain spends energy on its three major activities. Scientists had believed brain cells spend about 45 percent of their energy generating nerve impulses and 45 percent on postsynaptic potentials—electrical changes related to communications received from other neurons—and the remainder managing neurotransmitters. The new figures suggest that only about 15 percent of the energy goes to action potentials and nearly three-quarters to postsynaptic activity.
This has particular importance for understanding what we see during brain scans. Most brain scan techniques, including functional magnetic resonance imaging (fMRI), do not directly measure the brain’s electrical activity but rather the blood flow that supplies energy to nerve cells.
“There’s been a long debate about what you see in an fMRI signal—whether it’s a higher rate of firing or more postsynaptic activity,” Magistretti says.” Of course these are a bit related, but the upside is that we are seeing mostly the postsynaptic potentials,” the workings of the brain, not just its communications. This provides a more precise explanation for what fMRI scans show, he adds, but it remains to be seen whether it will affect how researchers conduct or interpret scans.
According to Alle, the dramatic difference between the squid and rat results also demonstrates the importance energy efficiency has played in the evolution of mammal brains—including our own.
“Of course one must be cautious, but as cortical neurons in rodents and humans are very similar in their electrical properties, and genes coding for ion channels are conserved across mammalian species, our results should also apply to humans,” he says. “The way our brain is built indicates that energy constraints have played an important role in its design.”