Novel Neurons

What makes up your mind?

Nothing is closer to us than our brains, but their complicated workings make understanding them no easy task. Billions of specialized cells called neurons work together, each using a combination of electrical and chemical signals to communicate with each other. Tiny gears in one of the universe’s most complex clocks, these cells weave together into the beautiful, lumpy organ that sits between your ears. If you’re confused about how things like basket cells and medium spiny neurons can be the building blocks of your very consciousness, you’re not alone. Neuroscience is a field dedicated to answering this question, and another recently discovered, colorfully named neuron may change neuroscientists’ approach.

The use of mouse models has been common in the study of neurological diseases for decades, and for good reason. Mice and humans are both mammals and share many genes, with both of their brains having many of the same neurological circuits. Additionally, and most importantly, mouse brains can be readily altered on the genomic, biochemical, and physical level for the sake of a study. However, there are limitations. From disease symptoms to cortex structure, there are differences between mouse and human brains that make it difficult to translate the results of mouse brain studies to human neurology. A recent collaborative study between the Allen Institute and the University of Szeged shows that an even more basic difference may lie in the cellular makeup of the two brains. The study, led by Ed Lein of the Allen Institute for Brain Science and Gabor Tamas of the University of Szeged, provides transcriptomic and morphophysiological evidence—that is, relating to a cell’s genes, shape, and firing properties—for the existence of a type of neuron not found in mouse brains.

In a fortunate coincidence, the two teams converged on the same discovery. The Allen Institute had been profiling the genetics of the neurons in the outermost layer of the human neocortex, the part of the brain dedicated to higher reasoning functions like cognition, spatial reasoning, and language, using a technique called single nucleus RNA sequencing. They separated the cells of the neocortex, isolated the nuclei in different tubes, and profiled the genes present, giving them a readout of what genes are turned on in each of the cells.

At the same time, the University of Szeged had been profiling the same region based on cell morphology and electrical behavior. The morphology or shape of a neuron can give insight into what other neurons it is interacting with, while the electrical properties, like how fast the neuron sends signals, can tell us how the cell processes signals in the overall neurological circuit of the brain.

It was only after the two groups came into contact with each other that they realized that they had characterized the same novel cell, dubbed the “rose hip cell” after its compact, bushy shape.

Further investigation found that this cell had not been found in mice brains, and while the specific function of the cell has yet to be determined, its existence has implications for how neuroscientists study neurological processes in the future. “Human brains aren’t just larger mouse brains,” said Trygve Bakken, a lead author on the study. Even though mouse models have helped neuroscientists study the human brain, the fact that there are differences between the two brains at the very cellular level could act as a catalyst to promote a shift from the traditional mouse models to more analogous neurological models. These could be brain samples from nonhuman primates or artificially cultured cerebral organoids, both of which could potentially serve to model the neurological processes that mice may be unable to.

Cognitive science, the study of how we think and process information, is an interdisciplinary field. Neuroscientists, biologists, psychologist, and many other scientists come together to try and solve the puzzle of our mind; when a major discovery in one field is made, the effects of that discovery can ripple through other fields, changing their approach to the brain. While the rose hip cell’s effect on our cognition is not yet known, its discovery could potentially mark the beginning of an era of increased understanding of what makes up the human brain, and what makes it special. “We’re on a new threshold of understanding not just for the rose hip cells, but for all the different types of neurons in the brain—what are their characteristics, how similar are they to those of the mouse, and that is going to allow us to untangle how they are all interconnected, and ultimately how the circuit works,” Bakken said.