Comparison of Neurons Across Species: Why Are Humans Different?

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Exciting study uncovers a key factor that sets human neurons apart from those of other mammals. koto_feja / Getty Images
  • A group of researchers have found that human neurons have far fewer ion channels than other mammalian neurons.
  • The lower density of ion channels may contribute to more efficient brain function in humans.
  • The findings of neuroscientists pave the way for future research into the evolutionary forces behind this distinction.

Neurons are the building blocks of the central nervous system, which includes the brain and the spinal cord. They share information via electrical impulses and chemical signals.

The human brain contains approximately 100 billion of these cells.

Neural impulses are generated by the activity of ion channels, which control the movement of mineral ions, including potassium and sodium. Typically in the mammalian brain, as the size of the neurons increases, the density of the ion channels in the neurons also increases.

To the surprise of neuroscientists at the Massachusetts Institute of Technology, Cambridge, and Harvard Medical School, Boston, this was not the case with human neurons.

Their research appears in a November 2021 edition of Nature.

Lou Beaulieu-Laroche, Ph.D., neuroscientist and lead author of the study, explained in a recent article on LinkedIn: “These findings have important implications for understanding our exceptional cognitive abilities and challenges. [that] therapies derived from animal models confronted in human clinical trials.

Dr Beaulieu-Laroche qualifies this article as “the highest scientific achievement”.

Neuronal size determines neurons enter exit characteristics – what is the probability that a neuron will “fire” after a certain level of input from other neurons. The size of neurons also varies considerably among mammalian species.

The research team analyzed brain samples from people with epilepsy who had undergone neurosurgery, Etruscan shrews, mice, rabbits and macaques, among other mammals.

The researchers aimed to “characterize Layer 5 cortical pyramidal neurons across 10 mammalian species to identify the allometric relationships that govern how neuronal biophysics change with cell size.

The authors chose this population of neurons because they are “reliably identifiable”, and scientists have studied them extensively. Allometry is the study of how an animal’s characteristics change with size.

By studying 10 species, the researchers were able to analyze various neuronal sizes and cortical thicknesses across the mammalian kingdom.

In particular, the researchers focused on two types of ion channels: cyclic nucleotide channels (HCN) activated by hyperpolarization and voltage-gated potassium channels. They focused on these two because they are relatively easy to access and have a strong influence on neural networks.

Neuroscientists have observed a consistent “building plan” with all species except humans. They write:

“In 9 of the 10 species, we observe conserved rules that control the conductance of voltage-gated potassium and HCN channels. Species with larger neurons, and therefore a reduced surface area / volume ratio, exhibit higher membrane ionic conductances.

In this context, conductance describes the ability of ions to easily cross a neuron’s membrane through ion channels.

Dr. Beaulieu-Laroche and his colleagues have found that human neurons do not exhibit the same allometric patterns as those of the other nine mammals. Instead, the conductances of voltage-gated potassium and HCN channels were much lower in human neurons.

These results demonstrate “conserved evolutionary principles for neuronal biophysics in mammals, as well as notable features of the human cortex”.

Several of the authors of this study had noted in previous research that human neurons are larger than those of other mammals.

However, current findings indicate that human layer 5 neurons “aren’t just big. […] but are fundamentally distinct.

Medical News Today discussed the current study with Keiland Cooper, Ph.D., neuroscientist at the University of California, Irvine. He did not participate in this research.

Dr. Cooper was intrigued that human neurons in layer 5 were distinct in terms of ion channels. He speculated: “Maybe the human brain is deviating from the model to meet a changing energy demand, as opposed to other species.”

Dr. Beaulieu-Laroche and his co-authors believe that the lower membrane conductance of human neurons allows the Cerebral cortex “Allocate energy resources to other aspects of neural function (eg, synaptic transmission) that are more computationally efficient.” “

In other words, the energy saved by harboring fewer ion channels could help the human brain perform other, more complex tasks.

According to its authors, this study provides “an important new place for future investigations into the human condition”.

Neuroscientists hope to explore where the extra energy of human neurons goes. They also want to determine if there are certain genetic changes that allow human neurons to become so efficient.

In addition, these researchers wonder if primates closely related to humans also have a lower ion channel density.

Dr. Cooper anticipates these findings as well, as he shared with MNT:

“Interspecies studies like these are great and, due to methodological challenges, are done much less often than they probably should be. “

“A study like this will open up a whole new set of questions that will need to be investigated: What might underlie the differences between humans and other species? Are there specific genetic markers or developmental milestones where species diverge? What could be the functional implications, or does the brain somehow compensate? ”

Dr Cooper added: “I am really delighted to see the follow-up work that will result from this study. “

Researchers do not yet understand why “[ion] conductance by volume is lower in humans, or why it is conserved in all other species tested. It will take a lot more investigation.

As for the limitations, the researchers point out that the history of the disease and the treatments of the humans behind the samples may have influenced the results of this study.

However, they note that “previous studies with extensive patient histories and types of surgery failed to observe significant correlations between disease etiology and dendritic morphology or synaptic plasticity.”

On this point, Dr. Cooper agrees; he said MNT, “I think the authors create a compelling case for human neurons to be representative, however, more work to dissociate these differences will need to be done to confirm this single study.”

As for the next steps, the authors conclude their article by noting:

“Exciting future work is needed to determine the evolutionary pressures underlying these distinctive features and their contribution to human brain function.”

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