Scientists identify a new kind of human brain cell
鈥楻osehip鈥� neurons not found in rodents, may be involved in fine-level control between regions of the human brain
One of the most intriguing questions about the human brain is also one of the most difficult for neuroscientists to answer: What sets our brains apart from those of other animals?
鈥淲e really don鈥檛 understand what makes the human brain special,鈥� said , Investigator at the Allen Institute for Brain Science. 鈥淪tudying the differences at the level of cells and circuits is a good place to start, and now we have new tools to do just that.鈥�
In a new published today in the journal Nature Neuroscience, Lein and his colleagues reveal one possible answer to that difficult question. The research team, co-led by Lein and , a neuroscientist at the University of Szeged in Szeged, Hungary, has uncovered a new type of human brain cell that has never been seen in mice and other well-studied laboratory animals.
Tama虂s and University of Szeged doctoral student Eszter Boldog dubbed these new cells 鈥渞osehip neurons鈥� 鈥� to them, the dense bundle each brain cell鈥檚 axon forms around the cell鈥檚 center looks just like a rose after it has shed its petals, he said. The newly discovered cells belong to a class of neurons known as inhibitory neurons, which put the brakes on the activity of other neurons in the brain.
The study hasn鈥檛 proven that this special brain cell is unique to humans. But the fact that the special neuron doesn鈥檛 exist in rodents is intriguing, adding these cells to a very short list of specialized neurons that may exist only in humans or only in primate brains.
The researchers don鈥檛 yet understand what these cells might be doing in the human brain, but their absence in the mouse points to how difficult it is to model human brain diseases in laboratory animals, Tama虂s said. One of his laboratory team鈥檚 immediate next steps is to look for rosehip neurons in postmortem brain samples from people with neuropsychiatric disorders to see if these specialized cells might be altered in human disease.
When different techniques converge
In their study, the researchers used tissue samples from postmortem brains of two men in their 50s who had died and donated their bodies to research. They took sections of the top layer of the cortex, the outermost region of the brain that is responsible for human consciousness and many other functions that we think of as unique to our species. It鈥檚 much larger, compared to our body size, than in other animals.
鈥淚t鈥檚 the most complex part of the brain, and generally accepted to be the most complex structure in nature,鈥� Lein said.
Tama虂s鈥� research lab in Hungary studies the human brain using a classical approach to neuroscience, conducting detailed examinations of cells鈥� shapes and electrical properties. At the Allen Institute, Lein leads a team working to uncover the suite of genes that make human brain cells unique from each other and from the brain cells of mice.
Several years ago, Tama虂s visited the Allen Institute to present his latest research on specialized human brain cell types, and the two research groups quickly saw that they鈥檇 hit on the same cell using very different techniques.
鈥淲e realized that we were converging on the same cell type from absolutely different points of view,鈥� Tama虂s said. So they decided to collaborate.
The Allen Institute group, in collaboration with researchers from the 小蓝俱乐部, found that the rosehip cells turn on a unique set of genes, a genetic signature not seen in any of the mouse brain cell types they鈥檝e studied. The University of Szeged researchers found that the rosehip neurons form synapses with another type of neuron in a different part of the human cortex, known as pyramidal neurons.
This is one of the first studies of the human cortex to combine these different techniques to study cell types, said , Senior Scientist at the Allen Institute for Brain Science and an author on the study.
鈥淎lone, these techniques are all powerful, but they give you an incomplete picture of what the cell might be doing,鈥� Hodge said. 鈥淭ogether, they tell you complementary things about a cell that can potentially tell you how it functions in the brain.鈥�
How do you study humanity?
What appears to be unique about rosehip neurons is that they only attach to one specific part of their cellular partner, indicating that they might be controlling information flow in a very specialized way.
If you think of all inhibitory neurons like brakes on a car, the rosehip neurons would let your car stop in very particular spots on your drive, Tama虂s said. They鈥檇 be like brakes that only work at the grocery store, for example, and not all cars (or animal brains) have them.
鈥淭his particular cell type 鈥� or car type 鈥� can stop at places other cell types cannot stop,鈥� Tama虂s said. 鈥淭he car or cell types participating in the traffic of a rodent brain cannot stop in these places.鈥�
The researchers鈥� next step is to look for rosehip neurons in other parts of the brain, and to explore their potential role in brain disorders. Although scientists don鈥檛 yet know whether rosehip neurons are truly unique to humans, the fact that they don鈥檛 appear to exist in rodents is another strike against the laboratory mouse as a perfect model of human disease 鈥� especially for neurological diseases, the researchers said.
鈥淥ur brains are not just enlarged mouse brains,鈥� said , Senior Scientist at the Allen Institute for Brain Science and an author on the study. 鈥淧eople have commented on this for many years, but this study gets at the issue from several angles.鈥�
鈥淢any of our organs can be reasonably modeled in an animal model,鈥� Tama虂s said. 鈥淏ut what sets us apart from the rest of the animal kingdom is the capacity and the output of our brain. That makes us human. So it turns out humanity is very difficult to model in an animal system.鈥�
Other co-authors on the study include Jennie Close, Song-Lin Ding, Jeremy Miller, Soraya Shehata, Kimberly Smith, Susan Sunkin and Abby Wall of the Allen Institute for Brain Science; Judith Baka, Sa虂ndor Borde虂, No虂ra Farago虂, A虂gnes K. Kocsis, Bala虂zs Kova虂cs, Ga虂bor Molna虂r, Ga虂spa虂r Ola虂h, Attila Ozsva虂r, Ma虂rton Ro虂zsa and Pa虂l Barzo虂 of the University of Szeged; Mark Novotny, Brian Aevermann, Francisco Diez-Fuertes, Jamison McCorrison, Danny Tran, Pratap Venepally, Roger Lasken, Nicholas Schork and Richard Scheuermann of the 小蓝俱乐部; La虂szlo虂 Puska虂s of the Hungarian Academy of Sciences; and Frank Steemers of Illumina, Inc