By Katherine Wright
The brain’s information transmitters, known as neurons, can be classified by looking at how they “talk” to each other, and this information is genetically encoded in the neuron, according to a study accepted for publication in an upcoming issue of the journal Cell. The finding by scientists at Cold Spring Harbor Laboratory provides a route to distinguishing neuron-types, a key puzzle piece in understanding how the brain’s information circuits function.
“The fundamental units [of the brain] are nerve cells,” Z. Josh Huang, a professor at Cold Spring Harbor and one of the study’s researchers, said. “There are billions of them and they all work together to produce cognition.”
However, while scientists know broadly what cells the brain contains, they don’t have a good way of distinguishing variations in these cells, Huang said. For example, are the cells all one type, or are there lots of different kinds of neurons?
“If you want to understand how the brain functions you need to know the parts list that make up this tissue,” Anirban Paul, another of the study’s researchers, said. “But unlike the definition a neuron there is really no definition for a neuron type,” Paul said, something he and his colleagues set out to address.
To study this question, the team sequenced the genes of a set of six mice neurons that were already thought to possibly be distinct types due to visible differences in the neuron’s shapes, and in how they connect with and send signals to other cells. The gene sequences were then plugged into a machine-learning algorithm that they used to search for patterns and differences in the neuron’s genome.
For each pattern the team asked: Is this set of genes sufficient to tell these neurons apart? If the answer was no, they moved on to the next pattern. “We literally negated 95% of the gene families [this way],” said Paul.
Using this method, the researchers found that just 40 gene families, out of more than 600 found in these neurons, were needed to distinguish the six neurons from one another, according to the research paper. Looking closely at these 40 families, they realized that all these genes were involved in the same function in the neurons, that of synaptic communication—how neurons send messages to each other.
“What we discovered is that the genes that enable these neurons to talk to each other are where differences arise,” said Paul. “[The discovery] has a huge implication going forward to finding further new [neuron] cell types.”
“[The result] is a masterpiece of science” Henry Markram, a professor at Swiss Federal Institute of Technology in Lausanne, Switzerland, who studies the brain, said. Markram was not involved in this research study. “It also provides the kind of data and insight that will allow us to build biologically accurate neuron models.”
Not only could this finding allow scientists to answer fundamental questions about how the brain functions, it could also help in understanding why it sometimes fails, for example in brain disorders like schizophrenia, autism, and epilepsy, Huang said. “In almost all disorders…its never a generalized brain degeneration. Its almost always certain parts of the brain and certain types of cells that are defective that effect the brain wiring and function.”
Being able to identify the specific neuron type that has stopped functioning as it should, could help in developing more effective treatments for these brain disorders with fewer side effects, Huang said. “Drugs that effect all the [brain’s] cells have tremendous side effects and are also ineffective. If we can identify the cells that are specifically affected, we can first try to understand how the neurocircuits and communications are affected and then potentially design strategies to specifically treat those cells.”