Author: Liu Fang
Editor: Kou Jianchao
Typography: Li Xuewei
Are the brain circuits of people and monkeys the same?
What makes people rich in emotions and self-awareness?
In medical experiments, can the same effect be achieved by replacing the human brain with monkey brain or mouse brain?
From daily joys and sorrows to major decisions in life, the fate of human beings is closely related to this magical organ of the brain.
It is this unique, mysterious brain, with an average weight of about 1.2-1.4 kg, that distinguishes humans from other animals and establishes human civilization. Neuroscientists estimate that the human brain has up to 100 billion neurons.
In traditional research, scientists have compared humans and other mammals primarily in terms of the size, weight, and structure of their brains, but still can't explain why humans' cognitive abilities are different.
For example, in the past, humans and elephants were mammals, but why didn't elephants with more neurons evolve to be smarter?
Recently, the research team from MIT and its collaborators have given some clues to this series of problems.
Studies have shown that the biophysical properties of neurons in the human cerebral cortex do not conform to the general laws of other mammals. Compared to other mammals, the number of neuronal ion channels in the human cerebral cortex that allow the flow of calcium, potassium, and sodium plasma is much smaller than expected.
Lou Beaulieu-Laroche, first author of the paper, said: "Comparative studies have confirmed that although the human brain is constructed like other mammalian brains, human neurons are special."
On November 10, the paper was published in the journal Nature under the title "Allometric rules for mammalian cortical layer 5 neuron biophysics."
The first is different from the rat-headed rat brain ratio
The team's experiment comparing the human brain to other mammals began in 2018, and their first subject was mice.
They found that the dendrites of the fifth layer of the human cerebral cortex are less excitable and also longer than the dendrites of the mouse brain, a feature that changes the input-output properties of the human brain neuronal cell bodies and dendrites.
Figure| comparison of fifth-layer pyramidal neuron morphology in humans and 9 mammals (Source: the paper)
The so-called dendrite refers to multiple protruding tissues on neurons, named because of their dendritic shape.
For the brain, dendrites are key structures that transmit information between and within each neuron. It receives input from a chemical signal from a previous neuron, excites an action potential when the excitatory tipping point is reached, and transmits information.
The cerebral cortex of primates is generally divided into six layers, with the outermost layer, that is, the first layer, located under the skull, and the innermost layer, the sixth layer, located closest to the white matter.
The fifth layer of the team's study refers to the inner pyramidal cell layer, which contains large pyramidal neurons, the main excitatory neurons in the prefrontal cortex. Excitatory neurons can transmit information to neighboring cells, while inhibitory neurons are responsible for slowing or blocking the firing behavior of excitatory neurons.
The team's 2018 findings laid the groundwork for further comparison of human cerebral cortex neurons.
Schematic diagram of the neuronal signaling process | (Source: UCLA)
It is also different from other mammals
It is not enough to simply find differences between humans and mice on the fifth layer of pyramidal neurons.
In the latest study, the team compared 9 different mammalian and human fifth-layer pyramidal neurons in the hope of gaining a more comprehensive understanding of the biophysical laws of mammalian neurons.
In this experiment, the nine mammals that made outstanding contributions were: the small skunk (the smallest mammal), gerbils, mice, rats, guinea pigs, ferrets, rabbits, velvet monkeys and macaques. Human brain tissue, on the other hand, is removed from epileptic patients during brain surgery.
The study found that in these 9 mammals, the density of neuronal ion channels increased with the size of neurons. For example, the volume of neurons in the cerebellar melon of the small skunk is very small, while the individual neurons in the rabbit brain are much larger. So in the same volume of brain tissue, the baby skunk has a much more number of neurons than rabbits.
But because of the higher density of ion channels in rabbit neurons, the number of ion channels in the two rodents should be roughly the same within the same volume of brain tissue.
Figure| Comparison of input-output properties of dendrites (Source: Thesis)
After analyzing a dataset of 2250 patch-clamp records, the researchers confirmed that this pattern was adapted to the nine mammals in the experiment.
That is, in the same species, the number of ion channels under the fifth unit volume of the cerebral cortex is about the same, and the energy required is roughly equivalent, a phenomenon that neuroscientists call conservation conductance per unit brain volume.
However, the team was surprised to find that the human brain tissue slices in the experiment did not conform to this law, with the exception of the pyramidal neurons in the fifth layer of the human cerebral cortex.
Figure | mammalian cerebral cortex and neuron density number table (Source: the paper)
In general, ion channels have three important properties: conducting ions, identifying and selecting specific ions, and opening and closing according to specific electrical, mechanical, or chemical signals. Channels in nerves and muscles guide ions through cell membranes at breakneck speeds, providing a large amount of ion current: up to 100 million ions per second may pass through a channel.
Since ion channels are often the site of action of drugs, poisons or toxins, they play a vital role in both the physiology and pathophysiology of the nervous system.
The researchers believe that the reduction in the density of ion channels in the human brain may be the result of trade-offs made at the time of evolution. To reduce energy consumption, the human brain reduces the number of ion channels, allowing the brain to use energy for other things, such as creating more complex synaptic connections between neurons, or exciting action potentials at higher rates.
Of course, this theory has yet to be confirmed. But some of the big problems that the latest findings raise are:
Is the human brain fundamentally different from other mammals?
Is it scientific to extrapolate human psychological mechanisms based on the behavior of mammals?
Can pharmacological studies based on mice and macaques accurately reflect the operating mechanism of human brain neurons?
Getting to know the human brain has just begun
In fact, this is not the first study to challenge traditional neuronal theory. In recent years, a growing body of research has shown that the brain mechanisms of the human brain and other mammals are not the same.
In 2018, an international team led by the Allen Institute for Brain Science discovered a new type of human brain cell in the outermost layer of the cerebral cortex and called these new cells "rosehip neurons."
The most amazing thing is that this cell exists only in the human brain and has never been found in the brains of other animals.
It is estimated that rosehip neurons account for 10-15% of inhibitory neurons in the new cerebral cortex (Layer I), which has a strong inhibitory regulatory effect on excitatory input to the whole brain.
In addition, in 2019, researchers at institutions such as the Weizmann Institute of Science in Israel also found that neurons in the human brain processed information more efficiently, but neurons in monkey brains were more synchronized and stable.
The study believes that in the case of encountering a tiger, monkeys need their brains to always be able to respond stably to escape, and for more advanced people, the brain can synthesize more information about the environment and other aspects to make more thoughts.
Obviously, our understanding of the brain has only just begun.
Although models such as mice have made great contributions to human psychology and neurology, the uniqueness of neurons in the human cerebral cortex reflects the limitations of mammalian models.
Unlike other organs, the unique cognitive and emotional functions developed by the human brain pose a huge challenge for scientists.
But it is precisely because of this uniqueness that we are born to be human and different.
bibliography:
https://en.wikipedia.org/wiki/Human_brain
https://www.nature.com/articles/s41586-021-04072-3
https://www.sciencedaily.com/releases/2021/11/211110131613.htm
https://www.cell.com/cell/fulltext/S0092-8674(18)31106-1
https://zhuanlan.zhihu.com/p/93570240
https://www.nature.com/articles/s41593-018-0205-2
http://www.xinhuanet.com/science/2019-01/23/c_137764723.htm