January 26, 2023

Striking Difference Discovered Between Neurons of Humans and Other Mammals

One of the findings from that research study was that human neurons had a lower density of ion channels than neurons in the rat brain. The scientists were shocked by this observation, as ion channel density was usually presumed to be constant throughout types. In their new research study, Harnett and Beaulieu-Laroche decided to compare neurons from several various mammalian types to see if they might discover any patterns that governed the expression of ion channels. They studied two types of voltage-gated potassium channels and the HCN channel, which conducts both potassium and sodium, in layer 5 pyramidal neurons, a type of excitatory nerve cells found in the brains cortex.
“What it looks like the cortex is attempting to do is keep the numbers of ion channels per system volume the same throughout all the types.

Human nerve cells have less ion channels, which may have allowed the human brain to divert energy to other neural processes.
Neurons interact with each other through electrical impulses, which are produced by ion channels that control the circulation of ions such as potassium and salt. In an unexpected new finding, MIT neuroscientists have actually revealed that human neurons have a much smaller sized number of these channels than expected, compared to the nerve cells of other mammals.

The scientists hypothesize that this decrease in channel density may have helped the human brain evolve to operate more efficiently, enabling it to divert resources to other energy-intensive procedures that are required to perform complex cognitive tasks.
” If the brain can save energy by decreasing the density of ion channels, it can invest that energy on other neuronal or circuit procedures,” states Mark Harnett, an associate professor of brain and cognitive sciences, a member of MITs McGovern Institute for Brain Research, and the senior author of the research study.
MIT neuroscientists evaluated pyramidal neurons from a number of different mammalian species, consisting of, from left to right, ferret, guinea pig, rabbit, marmoset, macaque, and human. Credit: Courtesy of the researchers
Harnett and his coworkers examined neurons from 10 different mammals, the most comprehensive electrophysiological study of its kind, and determined a “structure plan” that is true for every single types they took a look at– except for people. They found that as the size of nerve cells boosts, the density of channels discovered in the neurons likewise increases.
However, human neurons proved to be a striking exception to this guideline.
” Previous relative studies established that the human brain is built like other mammalian brains, so we were amazed to find strong evidence that human nerve cells are unique,” says former MIT college student Lou Beaulieu-Laroche.
Beaulieu-Laroche is the lead author of the study, which was published on November 10, 2021, in Nature.
A building plan
Neurons in the mammalian brain can get electrical signals from thousands of other cells, which input figures out whether they will fire an electrical impulse called an action potential. In 2018, Harnett and Beaulieu-Laroche discovered that human and rat neurons differ in a few of their electrical homes, mainly in parts of the neuron called dendrites– tree-like antennas that get and process input from other cells.
One of the findings from that research study was that human nerve cells had a lower density of ion channels than neurons in the rat brain. They studied 2 types of voltage-gated potassium channels and the HCN channel, which carries out both potassium and salt, in layer 5 pyramidal neurons, a type of excitatory nerve cells found in the brains cortex.
They were able to obtain brain tissue from 10 mammalian species: Etruscan shrews (one of the tiniest known mammals), gerbils, mice, rats, Guinea pigs, ferrets, macaques, marmosets, and rabbits, as well as human tissue gotten rid of from clients with epilepsy throughout brain surgical treatment. This range enabled the researchers to cover a range of cortical thicknesses and nerve cell sizes throughout the mammalian kingdom.
The scientists discovered that in almost every mammalian species they looked at, the density of ion channels increased as the size of the nerve cells increased. The one exception to this pattern was in human neurons, which had a much lower density of ion channels than expected.
The boost in channel density throughout types was surprising, Harnett states, because the more channels there are, the more energy is needed to pump ions in and out of the cell. It began to make sense once the scientists started believing about the number of channels in the total volume of the cortex, he states.
In the small brain of the Etruscan shrew, which is loaded with extremely small neurons, there are more nerve cells in a provided volume of tissue than in the exact same volume of tissue from the rabbit brain, which has much larger neurons. Because the bunny nerve cells have a greater density of ion channels, the density of channels in a provided volume of tissue is the exact same in both species, or any of the nonhuman species the scientists examined.
” This structure plan corresponds across nine various mammalian types,” Harnett states. “What it appears like the cortex is attempting to do is keep the numbers of ion channels per unit volume the exact same across all the species. This means that for an offered volume of cortex, the energetic expense is the very same, a minimum of for ion channels.”
Energy performance
The human brain represents a striking discrepancy from this structure plan, nevertheless. Instead of increased density of ion channels, the scientists discovered a remarkable decline in the expected density of ion channels for a given volume of brain tissue.
The scientists think this lower density may have evolved as a way to use up less energy on pumping ions, which permits the brain to utilize that energy for something else, like creating more complex synaptic connections in between neurons or firing action potentials at a higher rate.
” We think that humans have progressed out of this structure plan that was previously limiting the size of cortex, and they found out a way to become more energetically efficient, so you spend less ATP per volume compared to other types,” Harnett states.
He now hopes to study where that additional energy may be going, and whether there are specific gene anomalies that help nerve cells of the human cortex accomplish this high performance. The scientists are likewise interested in exploring whether primate types that are more closely related to people show comparable decreases in ion channel density.
Referral: “Allometric guidelines for mammalian cortical layer 5 nerve cell biophysics” by Lou Beaulieu-Laroche, Norma J. Brown, Marissa Hansen, Enrique H. S. Toloza, Jitendra Sharma, Ziv M. Williams, Matthew P. Frosch, Garth Rees Cosgrove, Sydney S. Cash and Mark T. Harnett, 10 November 2021, Nature.DOI: 10.1038/ s41586-021-04072-3.
The research was funded by the Natural Sciences and Engineering Research Council of Canada, a Friends of the McGovern Institute Fellowship, the National Institute of General Medical Sciences, the Paul and Daisy Soros Fellows Program, the Dana Foundation David Mahoney Neuroimaging Grant Program, the National Institutes of Health, the Harvard-MIT Joint Research Grants Program in Basic Neuroscience, and Susan Haar.
Other authors of the paper consist of Norma Brown, an MIT technical associate; Marissa Hansen, a previous post-baccalaureate scholar; Enrique Toloza, a college student at MIT and Harvard Medical School; Jitendra Sharma, an MIT research study researcher; Ziv Williams, an associate teacher of neurosurgery at Harvard Medical School; Matthew Frosch, an associate professor of pathology and health sciences and technology at Harvard Medical School; Garth Rees Cosgrove, director of epilepsy and practical neurosurgery at Brigham and Womens Hospital; and Sydney Cash, an assistant professor of neurology at Harvard Medical School and Massachusetts General Hospital.

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