Validating a Neuron Identification Method

A crab’s nervous system could help scientists learn what causes single neurons in the human brain to become “out of whack,” which can contribute to the development of neurological diseases like Alzheimer’s disease. Knowing exactly how a single neuron among billions operates could help scientists to one day design innovative ways to prevent and treat neurological diseases, perhaps by using targeted therapies. The new research was published yesterday in PNAS.

For the study, the researchers worked to validate a popular research method called RNA sequencing that can be used to identify unknown neurons in the brain and sort them into various subtypes. “There are billions of neurons in the human brain, yet we still don’t know how many distinct types there are,” says senior author David Schulz of the University of Missouri-Columbia. “We are finally at a technological point where we can ask the incredibly complex question—what are the brain’s building blocks?”

Schulz believes the answer to that question will drive everything we know about diseases in the brain for the next 50 to 100 years. However, in order to answer that question, he said we must first know how neurons are different from one another—and how healthy neurons differ from diseased ones.

Using a crab’s nervous system as a model, the researchers compared and validated the results of previous human RNA sequencing methods. Since crabs have already identifiable subtypes of neurons, the researchers already knew what they were looking for. This meant that they were able to work backward from the published results and use the RNA sequencing method to validate those findings.

Schulz said he was both surprised and reassured by what they found. “If you don’t know what you are looking for in the complex human brain, then early efforts using RNA sequencing are going to need some refinement before we can answer this fundamental question,” he says. “This study is one of those refinements. Until we can understand each component, we can’t expect to take the brain apart and put it back together again in order to figure out how it works.”