New type of human brain cell has been identified

Rosehip neurons are found in humans, but not rats and mice.

Researchers in the United States and Hungary have identified a new type of human brain cell. Called rosehip neurons, they aren’t found in mice and rodents, pointing to how difficult it is to model human brain disorders in lab animals.

The teams behind the study initially began their research independently of each other. One group, at the Allen Institute for Brain Science, investigates the genes that make human brain cells unique. The other, at the University of Szeged in Hungary, examines the shapes and electrical properties of neurons. When the researchers met to discuss their work, they realized they were narrowing in on the same, previously unidentified cells and decided to collaborate.

We spoke with Trygve Bakken, a senior scientist at the Allen Institute who is one of the study’s authors, to learn more.

ResearchGate: How did you find this neuron?

Trygve Bakken: We surveyed neurons in layer 1 of human neocortex using two complementary techniques. At the Allen Institute, we used single nucleus RNA-sequencing to profile gene expression from individual cells isolated from post-mortem human brain donors.

In another approach, our collaborators in Gabor Tamas’ group in Hungary measured the electrical activity of individual neurons in slices of human neurosurgical tissue. After recording, these neurons were filled with a dye and their 3D shape was reconstructed.

Combining these approaches, we identified a novel, highly specialized type of inhibitory neuron with distinctive shape, firing properties, and gene expression profile. This “rosehip” interneuron has not been described in rodent brains.

RG: What do rosehip neurons do?

Bakken: Rosehips have a distinctive shape with compact, bushy axons that selectively connect to the dendrites of excitatory neurons in layers 2/3. They can inhibit electrical activity in these cells. Rosehips also express many genes not expressed by other interneurons in layer 1.

RG: Why are they called rosehip neurons?

Bakken: This continues a long tradition in neuroscience of naming neurons based on their shape. Tamas’ group thought that these neuron’s compact, busy axons resembled rosehips.

RG: Why is it significant that rosehip neurons aren’t found in rodents?

Bakken: Rodents are a powerful model organism for studying neural circuitry, but they can’t be used to study cell types that are not present in the rodent brain. If we ultimately want to understand how the human brain works, then we need to study human brain tissue and other more closely related species, such as non-human primates.

RG: Do you think any animals other than humans have rosehip neurons?

Bakken: There are other examples of cell types that are found in the human but not rodent brain, such as spindle neurons. Spindle neurons are also found in other highly social, large-brained mammals such as monkeys and dolphins, and it may be that rosehips are also found in these species. This could be tested by profiling cellular diversity in these species using the same single nucleus RNA-sequencing technique and seeing if an interneuron type shares a gene expression signature with rosehips.

RG: How is it possible that there was a type of human neuron we didn’t know about until now? 

Bakken: Rosehips are quite rare and are only 10-15 percent of layer 1 neurons. Also, human brain tissue has been less studied than rodent brains, because it’s more difficult to acquire. This is now changing with access to new technologies such as single nucleus RNA-sequencing that allows high-throughput, unbiased profiling of cellular diversity in banked post-mortem human tissue.

RG: How will the identification of rosehip neurons affect future research?

Bakken: We now know genes that are selectively expressed in rosehip interneurons, and this gives us a genetic hook to label these cell types and study and manipulate them in human tissue.

RG: Could there be applications for treating brain disorders?

Bakken: We are still trying to understand to what extent different neurological and psychiatric diseases are disorders of specific cell types. If rosehips are implicated in brain disorders, then it may eventually be possible to target this cell type for treatment.


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Featured image courtesy of the Tamas Lab, University of Szeged