Neurons (brain cells) carry information within the brain as well as between the brain and the rest of the nervous system. They communicate with each other using chemical signals, as well as by means of tiny electrical impulses that are generated by the movements of ions into and out of the cells.
Ions of potassium (K+) and sodium (Na+) enter and exit neurons by means of specific ion channels across the cell membranes. This movement causes a difference in charge between the outside and inside of the cell, which leads to the generation of a nerve impulse.
Previous research, conducted by Mark Harnett and Lou Beaulieu-Laroche in 2018, showed that human neurons have far fewer ion channels along their length than rat neurons have. This was a surprising finding as the scientists had assumed that ion channel density was constant between mammalian species.
The researchers decided to compare the density of ion channels in neurons from several different mammalian species to see if they could find any patterns in the expression of ion channels. They obtained brain tissue from 10 mammalian species for this investigation: Etruscan shrews (one of the smallest known mammals), gerbils, mice, rats, Guinea pigs, ferrets, rabbits, marmosets, and macaques, as well as human tissue removed from patients with epilepsy during brain surgery
The study focused on two types of voltage-gated potassium channels and the HCN channel, which conducts both potassium and sodium, in layer five pyramidal neurons, a type of excitatory neuron found in the brain’s cortex.
The researchers found a general trend, in the mammalian species they investigated, that the density of ion channels increased as the neurons got longer. This was unexpected as the more channels there are, the more energy is required to pump ions in and out of the brain cell. However, when they took into consideration the overall size of the cortex in the brain, the relationship made more sense.
For example, the tiny brain of the Etruscan shrew is tightly packed with very small neurons such that there are more neurons in a given volume of tissue than in the same volume of tissue from the rabbit brain, which has much larger neurons. But because the rabbit neurons are longer and have a higher density of ion channels, the density of channels in a given volume of tissue is the same in both species, or any of the nonhuman species the researchers analyzed.
The one exception to this pattern was in human neurons, which had a much lower density of ion channels than expected.
“Previous comparative studies established that the human brain is built like other mammalian brains, so we were surprised to find strong evidence that human neurons are special,” said former MIT graduate student Lou Beaulieu-Laroche.
“This building plan is consistent across nine different mammalian species,” says Harnett, an associate professor of brain and cognitive sciences, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study. “What it looks like the cortex is trying to do is keep the numbers of ion channels per unit volume the same across all the species. This means that for a given volume of cortex, the energetic cost is the same, at least for ion channels.”
Human brains make a striking exception to the above relationship. Instead of increased density of ion channels, the researchers found a dramatic decrease in the density of ion channels for a given volume of brain tissue. They believe that this lower density may be a response to energetic constraints; if less energy is expended on pumping ions across the membrane, the brain will be able to use that energy for something else, like creating more complicated connections between neurons or firing nerve impulses at a higher rate.
“If the brain can save energy by reducing the density of ion channels, it can spend that energy on other neuronal or circuit processes,” said Harnett. “We think that humans have evolved out of this building plan that was previously restricting the size of cortex, and they figured out a way to become more energetically efficient, so you spend less ATP per unit volume compared to other species.”
The experts said that research is needed to determine where the extra energy gets used, and whether there are specific gene mutations that help neurons of the human cortex achieve this high efficiency. In addition, they would like to investigate whether other primate species that are more closely related to humans show a similar reduction in ion channel density.
The research is published in the journal Nature.