Striking difference between neurons of humans and other mammals

Date:
November 10, 2021
Source:
Massachusetts Institute of Technology
Summary:
Human neurons have a lower density of ion channels than expected,
compared to neurons of other mammals, according to a new study. The
researchers hypothesize that a lower channel density may have
helped the human brain evolve to operate more efficiently.



FULL STORY ========================================================================== Neurons communicate with each other via electrical impulses, which are
produced by ion channels that control the flow of ions such as potassium
and sodium. In a surprising new finding, MIT neuroscientists have shown
that human neurons have a much smaller number of these channels than
expected, compared to the neurons of other mammals.


==========================================================================
The researchers hypothesize that this reduction in channel density
may have helped the human brain evolve to operate more efficiently,
allowing it to divert resources to other energy-intensive processes that
are required to perform complex cognitive tasks.

"If the brain can save energy by reducing the density of ion channels,
it can spend that energy on other neuronal or circuit processes," says
Mark 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.

Harnett and his colleagues analyzed neurons from 10 different mammals,
the most extensive electrophysiological study of its kind, and identified
a "building plan" that holds true for every species they looked at --
except for humans.

They found that as the size of neurons increases, the density of channels
found in the neurons also increases.

However, human neurons proved to be a striking exception to this rule.

"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," says former MIT graduate student Lou Beaulieu-Laroche.



========================================================================== Beaulieu-Laroche is the lead author of the study, which appears today
in Nature.

A building plan Neurons in the mammalian brain can receive electrical
signals from thousands of other cells, and that input determines whether
or not they will fire an electrical impulse called an action potential. In 2018, Harnett and Beaulieu- Laroche discovered that human and rat neurons differ in some of their electrical properties, primarily in parts of the
neuron called dendrites - - tree-like antennas that receive and process
input from other cells.

One of the findings from that study was that human neurons had a lower
density of ion channels than neurons in the rat brain. The researchers
were surprised by this observation, as ion channel density was generally assumed to be constant across species. In their new study, Harnett
and Beaulieu-Laroche decided to compare neurons from several different mammalian species to see if they could find 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 neurons
found in the brain's cortex.

They were able to obtain brain tissue from 10 mammalian species: 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. This variety
allowed the researchers to cover a range of cortical thicknesses and
neuron sizes across the mammalian kingdom.



==========================================================================
The researchers found that in nearly every mammalian species they looked
at, the density of ion channels increased as the size of the neurons
went up. The one exception to this pattern was in human neurons, which
had a much lower density of ion channels than expected.

The increase in channel density across species was surprising, Harnett
says, because the more channels there are, the more energy is required
to pump ions in and out of the cell. However, it started to make sense
once the researchers began thinking about the number of channels in the
overall volume of the cortex, he says.

In the tiny brain of the Etruscan shrew, which is packed with very small neurons, 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 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.

"This building plan is consistent across nine different mammalian
species," Harnett says. "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." Energy efficiency The
human brain represents a striking deviation from this building plan,
however. Instead of increased density of ion channels, the researchers
found a dramatic decrease in the expected density of ion channels for
a given volume of brain tissue.

The researchers believe this lower density may have evolved as a way
to expend less energy on pumping ions, which allows the brain to use
that energy for something else, like creating more complicated synaptic connections between neurons or firing action potentials at a higher rate.

"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 volume compared to other species," Harnett says.

He now hopes to study where that extra energy might be going, and whether
there are specific gene mutations that help neurons of the human cortex
achieve this high efficiency. The researchers are also interested in
exploring whether primate species that are more closely related to humans
show similar decreases in ion channel density.

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, and the Harvard-MIT
Joint Research Grants Program in Basic Neuroscience.

========================================================================== Story Source: Materials provided by
Massachusetts_Institute_of_Technology. Original written by Anne
Trafton. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. 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, Mark T. Harnett. Allometric rules
for mammalian cortical layer 5 neuron biophysics. Nature, 2021;
DOI: 10.1038/s41586- 021-04072-3 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211110131613.htm

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