Comparison of Primate Brains Reveals Why Humans Are Unique

The neurotransmitter dopamine appears to be central to human identity, but surprisingly links our brains with those of macaques.

Since humans and chimpanzees split from their common ancestor around 6 million years ago, the Homo sapiens brain and that of our closest primate relative evolved on their own separate paths.

Besides the obvious size difference — the human brain is about three times larger than the chimp brain — little has been known about how the human brain and the rest of the nervous system changed in our lineage over evolutionary time.

A new evaluation of brain tissue samples from various primates identified key elements that make the human brain unique, including cortical circuits underlying production of the neurotransmitter dopamine. The findings are published in the journal Science.

"Based on our data, which is comprised of gene expression across 16 brain regions, we found that the most distinct region, i.e. the region where we observe more human-specific differences in gene expression, is the striatum, a region involved in motor coordination, reward, and decision-making," lead author André M. Sousa of the Yale School of Medicine and the Kavli Institute for Neuroscience told Seeker.

The study looked at transcriptional profiles of 247 tissue samples from six humans, five chimps, and five macaques. While they were not surprised to identify greater difference between human and macaque brains than between human and chimp brains, the researchers were astounded by a feature that links humans to monkeys.

Sousa, senior author Nenad Sestan, and their team found a rare population of interneurons that produce dopamine and is enriched in the human striatum, but did not make a similar finding in chimp, bonobo, or gorilla brains.

"Surprisingly, this population of cells is also present in macaques and several other primate species that are not among the non-human African great apes," Sestan told Seeker. "The implication is that these cells were somehow lost in the lineage leading to the African great apes and recovered specifically in the human lineage."

The finding shows that this population of cells in the human brain is more similar to that of a macaque than a chimp brain.

How the other great apes lost the cells remains unknown, but the researchers theorize genetic disruptions affecting the cells' migration to different parts of the brain, differentiation, or survival could have led to the loss.

Sestan explained that, like a city, the brain is a highly organized arrangement of discrete units linked by transportation and communication systems. In the brain, cells are among the units, migratory pathways are the highways or roads, and various electrical or chemical signals, including dopamine, are the communication systems.

Similar to a city’s real estate industry, the three most important things are location, location, location.

"Very few neurons born in the developing brain reside in the same location in the adult," Sestan said. "Instead, they are born, migrate to a new location, establish functionality, and then, eventually die. As you might expect, a lot can go wrong. A cell might not be born or might die prematurely, it might migrate to the wrong location, or it might assume or acquire a different functionality."

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These events could then help to explain why the brain differences exist between humans and chimps, with which we share up to 98 percent of the same DNA. "In principle,” Sestan said, “small changes in the wiring of the brain can lead to profound and specific functional changes."

Human brain interneurons express the enzymes tyrosine hydroxylase (TH) and DOPA (3,4-dihydroxyphenylalanine) decarboxylase (DDC). The two proteins are involved in dopamine biosynthesis.

While the ancestors of chimps and gorillas lost the ability to express these enzymes in the neocortex, a human ancestor likely recovered it. The scientists do not know which human ancestor recovered this ability, or when.

Since dopamine in the midbrain plays many roles in the central nervous system tied to cognition and behavior, humans would seem to have won the evolutionary brain jackpot. The definition of intelligence is subjective, but our working memory, reflective exploratory behavior, and other cognitive skills appear to be uniquely enhanced versus these abilities in other animals.

"After all, to the best of our knowledge, we are the only living species that is trying to understand how our brain works and what makes our brain different from other species' brains," Sousa said.

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On the other hand, there appear to be drawbacks associated with the structure and organization of the human brain.

"In general, the additional brain size and connectivity of the human brain compared to the chimpanzee or macaque, along with the protracted period of time during which human neurodevelopment occurs, means that there are many more problems than can arise and a greater period of time during which those problems can occur," Sestan explained.

Prior research, for example, determined that dopamine-producing neurons throughout the brain are damaged in Parkinson's disease. In fact, Parkinson's patients often receive L-DOPA, an amino acid produced by TH. DDC may then produce dopamine using L-DOPA as a substrate.

Comparisons of primate brains can therefore reveal differences that may prove relevant for disease therapeutics, as well as gaining a better understanding of human cognition and behavior and what makes us unique among other primates.

Sestan admits that he and his international team began the experiments thinking they might not observe significant findings. “That is the nature of basic research,” he said. “You don’t know what is truly important until you take a good, long look at it, and a lot of times you first have to spend time just learning where to look."

Currently, the researchers are studying the function of several genes with human-specific expression patterns. Sousa said, "The function of most of these genes in the brain is yet to be uncovered."

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