Yale Scientists Discover Clues to What Makes the Human Brain Different
What distinguishes the human brain from that of all other animals — including even our closest primate relatives? Yale researchers identified species-specific — particularly human-specific — features in an analysis of cell types in the prefrontal cortex of four primate species. They reported their findings on August 25, 2022, in the journal Science.
What they found that makes us human may also make us susceptible to neuropsychiatric diseases.
For the study, the scientists looked specifically at the dorsolateral prefrontal cortex (dlPFC). This is a brain region that is unique to primates and essential for higher-order cognition. Using a single cell RNA-sequencing technique, the researchers profiled expression levels of genes in hundreds of thousands of cells collected from the dlPFC of adult humans, chimpanzees, macaque, and marmoset monkeys.
... “Today, we view the dorsolateral prefrontal cortex as the core component of human identity, but still we don’t know what makes this unique in humans and distinguishes us from other primate species,” said Nenad Sestan. He is the lead senior author of the paper, the Harvey and Kate Cushing Professor of Neuroscience at Yale ... To answer this, the scientists first asked whether there are there any cell types uniquely present in humans or other analyzed non-human primate species. After grouping cells with similar expression profiles they revealed 109 shared primate cell types. They also discovered five that were not common to all species. These included a type of microglia, or brain-specific immune cell, that was present only in humans and a second type shared by only humans and chimpanzees.
The human-specific microglia type exists throughout development and adulthood, the researchers found. This suggests that the cells play a role in the upkeep and maintenance of the brain rather than combatting disease.
“We humans live in a very different environment with a unique lifestyle compared to other primate species; and glia cells, including microglia, are very sensitive to these differences,” Sestan said. “The type of microglia found in the human brain might represent an immune response to the environment.”
Another human-specific surprise was revealed in an analysis of gene expression in the microglia — the presence of the gene FOXP2. This discovery raised great interest among researchers because variants of FOXP2 have been linked to verbal dyspraxia, a condition in which patients have difficulty producing language or speech. Other research has also shown that FOXP2 is associated with other neuropsychiatric diseases, such as autism, schizophrenia, and epilepsy. “FOXP2 has intrigued many scientists for decades, but still we had no idea of what makes it unique in humans versus other primate species,” said Shaojie Ma. He is a postdoctoral associate in Sestan’s lab and co-lead author. We are extremely excited about the FOXP2 findings because they open new directions in the study of language and diseases.”
What distinguishes the human brain from that of all other animals — including even our closest primate relatives? Yale researchers identified species-specific — particularly human-specific — features in an analysis of cell types in the prefrontal cortex of four primate species. They reported their findings on August 25, 2022, in the journal Science.
What they found that makes us human may also make us susceptible to neuropsychiatric diseases.
For the study, the scientists looked specifically at the dorsolateral prefrontal cortex (dlPFC). This is a brain region that is unique to primates and essential for higher-order cognition. Using a single cell RNA-sequencing technique, the researchers profiled expression levels of genes in hundreds of thousands of cells collected from the dlPFC of adult humans, chimpanzees, macaque, and marmoset monkeys.
... “Today, we view the dorsolateral prefrontal cortex as the core component of human identity, but still we don’t know what makes this unique in humans and distinguishes us from other primate species,” said Nenad Sestan. He is the lead senior author of the paper, the Harvey and Kate Cushing Professor of Neuroscience at Yale ... To answer this, the scientists first asked whether there are there any cell types uniquely present in humans or other analyzed non-human primate species. After grouping cells with similar expression profiles they revealed 109 shared primate cell types. They also discovered five that were not common to all species. These included a type of microglia, or brain-specific immune cell, that was present only in humans and a second type shared by only humans and chimpanzees.
The human-specific microglia type exists throughout development and adulthood, the researchers found. This suggests that the cells play a role in the upkeep and maintenance of the brain rather than combatting disease.
“We humans live in a very different environment with a unique lifestyle compared to other primate species; and glia cells, including microglia, are very sensitive to these differences,” Sestan said. “The type of microglia found in the human brain might represent an immune response to the environment.”
Another human-specific surprise was revealed in an analysis of gene expression in the microglia — the presence of the gene FOXP2. This discovery raised great interest among researchers because variants of FOXP2 have been linked to verbal dyspraxia, a condition in which patients have difficulty producing language or speech. Other research has also shown that FOXP2 is associated with other neuropsychiatric diseases, such as autism, schizophrenia, and epilepsy. “FOXP2 has intrigued many scientists for decades, but still we had no idea of what makes it unique in humans versus other primate species,” said Shaojie Ma. He is a postdoctoral associate in Sestan’s lab and co-lead author. We are extremely excited about the FOXP2 findings because they open new directions in the study of language and diseases.”
When Our Eyes Move During REM Sleep, We’re Gazing at Things in the Dream World: Multiple Brain Regions Coordinate to Conjure Wholly Imagined Worlds
When our eyes move during REM sleep, we’re looking at things in the dream world our brains have created, according to a new study by researchers at the University of California, San Francisco (UCSF). The findings shed light not only on how we dream, but also on how our imaginations work.
REM sleep, which is named for the rapid eye movements associated with it, has been known since the 1950s to be the phase of sleep when dreams occur. But the purpose of the eye movements has remained a matter of much mystery and debate.
“We showed that these eye movements aren’t random. They’re coordinated with what’s happening in the virtual dream world of the mouse,” said Massimo Scanziani, PhD, senior author on the study, which was published in the August 25, 2022, issue of the journal Science.
“This work gives us a glimpse into the ongoing cognitive processes in the sleeping brain and at the same time solves a puzzle that’s triggered the curiosity of scientists for decades,” he said.
In the second half of the 20th century, some experts hypothesized that these REM movements may be following scenes in the dream world. However, there was little way to test this theory, and the experiments that could be done (noting a dreamers’ eye direction and then waking them up to ask where they were looking in the dream) provided contradictory results. Many scientists wrote off REM movements as random actions, perhaps to keep the eyelids lubricated. [But the new study was] able to look at “head direction” cells in the brains of mice, who also experience REM sleep. These cells act something like a compass, and their activity shows scientists which direction the mouse perceives itself as heading.
While monitoring the mouse’s eye movements, the team simultaneously recorded data from these cells about its heading directions. Comparing them, they discovered that the direction of eye movements and of the mouse’s internal compass were precisely aligned during REM sleep, just as they do when the mouse is awake and moving around.
...
Scanziani is interested in the “generative brain,” meaning the ability to make up objects and scenarios.
“One of our strengths as humans is this capacity to combine our real-world experiences with other things that don’t exist at the present moment and may never exist,” he said. “This generative ability of our brain is the basis of our creativity.” Scanziani noted that in a dream, you can combine familiar things with the impossible. He described a recurrent dream he had as a young diver, in which he was able to breathe underwater. Invariably, he woke up to find it wasn’t true. “But in the dream, you believe it’s real because there aren’t sensory inputs to bring you back to reality,” said Scanziani. “It’s a perfectly harmonious fake world.”
Scanziani’s research team discovered that the same parts of the brain — and there are many of them — coordinate during both dreaming and wakefulness, lending credence to the idea that dreams are a way of integrating information gathered throughout the day.
How those brain regions work together to produce this generative ability is the mystery that Scanziani plans to continue trying to unravel.
When our eyes move during REM sleep, we’re looking at things in the dream world our brains have created, according to a new study by researchers at the University of California, San Francisco (UCSF). The findings shed light not only on how we dream, but also on how our imaginations work.
REM sleep, which is named for the rapid eye movements associated with it, has been known since the 1950s to be the phase of sleep when dreams occur. But the purpose of the eye movements has remained a matter of much mystery and debate.
“We showed that these eye movements aren’t random. They’re coordinated with what’s happening in the virtual dream world of the mouse,” said Massimo Scanziani, PhD, senior author on the study, which was published in the August 25, 2022, issue of the journal Science.
“This work gives us a glimpse into the ongoing cognitive processes in the sleeping brain and at the same time solves a puzzle that’s triggered the curiosity of scientists for decades,” he said.
In the second half of the 20th century, some experts hypothesized that these REM movements may be following scenes in the dream world. However, there was little way to test this theory, and the experiments that could be done (noting a dreamers’ eye direction and then waking them up to ask where they were looking in the dream) provided contradictory results. Many scientists wrote off REM movements as random actions, perhaps to keep the eyelids lubricated. [But the new study was] able to look at “head direction” cells in the brains of mice, who also experience REM sleep. These cells act something like a compass, and their activity shows scientists which direction the mouse perceives itself as heading.
While monitoring the mouse’s eye movements, the team simultaneously recorded data from these cells about its heading directions. Comparing them, they discovered that the direction of eye movements and of the mouse’s internal compass were precisely aligned during REM sleep, just as they do when the mouse is awake and moving around.
...
Scanziani is interested in the “generative brain,” meaning the ability to make up objects and scenarios.
“One of our strengths as humans is this capacity to combine our real-world experiences with other things that don’t exist at the present moment and may never exist,” he said. “This generative ability of our brain is the basis of our creativity.” Scanziani noted that in a dream, you can combine familiar things with the impossible. He described a recurrent dream he had as a young diver, in which he was able to breathe underwater. Invariably, he woke up to find it wasn’t true. “But in the dream, you believe it’s real because there aren’t sensory inputs to bring you back to reality,” said Scanziani. “It’s a perfectly harmonious fake world.”
Scanziani’s research team discovered that the same parts of the brain — and there are many of them — coordinate during both dreaming and wakefulness, lending credence to the idea that dreams are a way of integrating information gathered throughout the day.
How those brain regions work together to produce this generative ability is the mystery that Scanziani plans to continue trying to unravel.
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