The brains of all mammals have a neocortex, made up of six layers of neurons that are responsible for complex calculations and connections that help improve cognitive abilities. Scientists are very interested in the phenomenon of non-mammalian brains not having a neocortex, and they are exploring how this complex part of the brain develops. Researchers are looking for information from the brains of reptiles because they are close relatives of mammals. The reptilian brain has three layers of structure called the vestricular ridge (DVR), which functionally resemble the neocortex. For the past five decades, evolutionary neuroscientists have debated whether the neocortex and DVR are derived from earlier simpler traits of a common ancestor of mammals and reptiles.
However, by studying the properties of unseen molecules, scientists have begun to question this view. Researchers at Columbia University have demonstrated by studying how genes are represented in individual brain cells that there is no direct link between reptilian DVRs and mammalian neocortices, despite structural similarities. Surprisingly, the cerebral cortex of mammals appears to be completely new, without any remnants of ancestral structures. It contains new neuronal types that are uncommon in early animals.
Last September, research led by evolutionary and developmental biologist Maria Antononiettatosches was published in the journal Science. This study shows that the brain's innovation in the evolutionary process is not limited to creating new components. Other studies published in the same issue of the journal Science by Toshs and his team have shown that even what looks like an ancient brain region is altered by integrating new cell types. The study of gene behavior has revealed significant differences between neurons. These findings have prompted researchers to rethink how to classify certain parts of the brain and to reassess whether certain animals have more complex brains than previously thought.
The famous neuroscientist Paul McKellen proposed the theory of brain evolution in the 60s of the 20th century. He believed that the basal ganglia were a group of structures at the base of the brain, the remnants of the reptilian "lizard brain" that was responsible for controlling behavior and survival instincts. Although this theory was later proven wrong, it had a significant impact on the brain. McLean believes that mammals have developed an limbic system above the basal ganglia that regulates mood. And in the evolution of higher mammals, such as humans, he proposed the theory of the neocortex, known as the "thinking cap", which occupies the top of the brain and promotes a higher level of cognition.
Carl Sagan drew a lot of attention with his 1977 Pulitzer Prize-winning book, The Dragon of Eden, which introduced the concept of the "Triune Brain." However, evolutionary neuroscientists are skeptical of this model. Research quickly disproved this model, finding that different regions of the brain did not always stack together over time during evolution. Paul Sisek, a cognitive neuroscientist at the University of Montreal, likens this process to the whole system evolving and adapting together, rather than just adding a new app to an iPhone, explaining that the brain evolves as a whole and that the old parts adapt to the addition of new parts.
Harvey Caton of the University of California, San Diego, is an evolutionary biologist who believes that the neocortex of mammals is similar to the DVR of reptiles, suggesting an evolutionary link between them. This is currently the most widely accepted theory about the emergence of new brain regions, which evolved mainly by replicating and altering existing structures and neural pathways. From an evolutionary point of view, they are considered homologous, meaning that they evolved from a common ancestor of mammals and reptiles.
However, researchers such as Luispuelles at the University of Mosia in Spain hold a different view. They found that reptiles and mammals have completely different developmental processes, and that neocortices and DVRs are formed differently. This suggests that the DVR and cerebral cortex may have evolved differently. Therefore, any similarities between them may be coincidental, influenced by the functions and limitations of these structures, rather than from a common ancestor.
The origins of the cerebral neocortex and DVR have been around for a long time, but now there is a new approach to solving this problem. Single-cell RNA sequencing technology allows scientists to analyze gene transcriptions that are active within a single cell. Evolutionary neuroscientists can uncover many complex differences between neurons by analyzing these gene expression profiles. They can use these differences to assess the evolutionary connections between neurons.
Try**Ebakken, a molecular neuroscientist at the Allen Institute for Brain Science, explains: "Measuring gene expression provides a clear advantage because we can make direct comparisons. "When we analyze the lizard's gene A and compare it to the mammalian gene A, we basically see a similar picture because they share a common evolutionary origin," he explained. "This technology marks a new phase in evolutionary neuroscience. According to Courtney Babbitt, an expert in evolutionary genomics at the University of Massachusetts in Amherst, it reveals previously unknown cell populations.
In 2015, Toshs was doing postdoctoral research work in the Gilles Laurent lab at the Max Planck Institute for Brain Research in Germany, where he was eager to delve deeper into the origins of the cerebral cortex using single-cell RNA sequencing technology, as the development of single-cell RNA sequencing technology has increased the ability to analyze cell samples tenfold. Three years later, Toshs and her team published their preliminary findings. They compared the neuronal cell types of turtles and lizards with the neuronal cell types of humans and mice. The DVR (frontal lobe of the brain) of reptiles and the neocortex of mammals evolved in different brain regions, suggesting that changes in gene expression suggest this.
Bradley Colquet, a molecular neuroscientist at the University of California, Santa Cruz, said: "2018 was an important milestone as it was the first to conduct extensive molecular analyses of nerve types in mammals and reptiles. However, Toshs and her team realized that it was important to understand how reptile and mammalian nerve cell types corresponded to neurons found in an ancient common ancestor to determine that the two brain regions did not come from the same ancestor.
Scientists chose to look for clues in the brains of sharp-edged salamanders because they are known for their ability to stick their ribs into ** as a defense. The sharp-edged salamander belongs to the amphibians, which later formed into different evolutionary branches. Scientists are trying to determine whether the neurons of the salamander's cerebral cortex (located in the front of the brain) and the neurons of the mammalian neocortex or reptilian DVR (located in the front of the brain) come from the same ancestor.
The Tosches team performed single-cell RNA sequencing of brain cells from a large number of salamanders in 2022, and they compared the new data with information previously collected from reptiles and mammals. The researchers carefully prepared and labeled the brains of small salamanders, which were only one-fifth the size of a mouse's brain. A shoebox-sized machine processes these prepared brains, efficiently preparing all the samples for sequencing in about 20 minutes. Torsés stressed that the process could have taken up to a year to make the same progress if earlier techniques had been used.
Through the analysis of the sequencing data, the resolution of the controversy became more apparent. Some neurons in axolotls are similar to those found in reptilian DVR, but others are less aligned. This suggests that some parts of the DVR evolved from the cerebral cortex of ancient ancestors shared by salamanders and reptiles.
In addition, Tosches and colleagues proposed that certain types of neurons evolved only in mammals. This is because certain cells in the neocortex, especially the pyramidal neurons that make up most of the neurons in this structure, are different from the cells of reptiles. Tosches and his team were the first to validate this idea using high-precision single-cell RNA sequencing, although the idea had been proposed by researchers before.
Although some parts of reptilian DVRs may have evolved from brain regions of ancient creatures, Toshs and her team claim that almost the entire neocortex of mammals is an evolutionary innovation. The neocortex of mammals emerges along with the flourishing of new types of cells. Georg Stridett, a neuroscience researcher at the University of California, Irvine, applauded the findings and said they were exciting and unexpected because they helped resolve the long-standing controversy that proves that the neocortex of mammals is not similar to the DVR of reptiles because they do not have a common origin.
Contrary to the Trinity Brain Theory, the Toshs team's new findings suggest that the neocortex of the mammalian brain is not just superimposed on older brain regions;Conversely, as the neocortex expands and new pyramidal neurons are formed, other brain regions are evolving in tandem. This suggests that the mammalian brain is more than just a "lizard brain". In fact, the increasing complexity within the neocortex may have driven the evolution of other parts of the brain, which may be contrary to what we previously knew. It's like a cogwheel where each part interacts and together drives the evolution of the brain.
In a recent study, Toshs and her colleagues found that ancient brain regions are still evolving. The study was published in the September 2022 issue of the journal Science. Toshs collaborated with postdoctoral supervisor Lauren on a comparative study of lizard and mouse brains, using single-cell RNA sequencing to uncover revelations between new and old cell types. First, they compared the nerve cell lineages of each species to determine common nerve cell types, meaning they had a common ancestor. After that, they took a closer look at the differences in nerve cell types and found differences between different species.
Their findings suggest that there are both traditional and novel nerve cell types not just in areas that are thought to be nearest, but throughout the brain. According to Johns Hopkins evolutionary neuroscientist Justuskebschull, there is a "mosaic" in the brain that includes both modern and medieval cell types. Still, Barbara Finley, an evolutionary neuroscientist at Cornell University, argues that ending the debate is not so simple. She argues that studying how neurons form, migrate and make connections during development is not just about comparing their position in the brains of adult amphibians, reptiles and mammals.
Toshs notes that amphibian brains may have lost some of the complexity that early common ancestors possessed during evolution. To test this idea, researchers need to sequence single-cell RNA from extant amphibians, such as primitive bony fishes. This study may shed light on the presence of certain neuronal types in early organisms that have their early forms in mammals. In addition, Toshs and her team are discussing the redefinition of the cerebral cortex and which animals possess the cerebral cortex, the current definition of which requires a visible neural layer similar to the neocortex or DVR. However, Toshs argues that this definition is outdated traditional neuroanatomical standards. Using new sequencing tools, they found evidence of the presence of a brain layer in the salamander brain.
On this issue, Toshs stressed that there is no reason to deny the cerebral cortex of salamanders or other amphibians. She suggested that if we apply the word "cortex" to the reptilian brain, then the cortex of the salamander brain should also be classified as cortex. Babbitt supports Tosh's view that the definition of classical morphology based on tradition may not be adapted to the development of modern tools. The debate also involves what neuroscientists think about birds. Although birds are on par with, or even surpass, many mammals in cognitive abilities, they are descendants of reptiles and do not display visible layered structures, similar to digital video recorders (DVRs), but these areas contain complex behaviors and skills in the bird's brain. However, there is no official acknowledgement that birds possess the cerebral cortex.
According to Stridter, the latest single-cell data from Tosches' team underscores an important concern: overemphasizing appearance can lead scientists to lose direction. This means that we can't determine homology between organisms based on appearance alone.
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