Just as stem cells start out as universal cells in the human embryo, prototypic neuron cells start out as undifferentiated neurons. Their fate is undetermined until the “notch” pathway tells them what flavor of a neuron to become ” inhibitory or excitatory. Until recently, scientists did not understand how neurons made this distinction as immature embryo cells.
Now, thanks to Martyn Goulding, Ph.D. at the Salk Institute, the “notch” pathway explains the fate of these tiny neurons.
Goulding’s lab studies genes that control development in vertebrates. These genes typically develop and create their functional cells in the spinal cord, the center of movement and touch in a body. There are two main questions addressed in the lab: How do genes control cell fate decisions? How do neurons get integrated into neural networks?
“What makes motor neurons versus some other type of, say, neuron in the nervous system” is an example of a specific questions about how genes affect cell fate decisions, Goulding stated. It is this question that led to the discovery of the notch pathway. However, to understand the function of the notch pathway, it is necessary to understand the basic science of a neuron.
“A neuron is an excitable cell “¦ it has a whole lot of processes which are called dendrites,” Goulding explained. “These dendrites actually allow the cell to make contact or to receive input from other nerve cells.”
The output side of the neuron is called the axon.
“Axon is a process or a number of processes that goes away from the cell “¦ but like a branch “¦ it will make contacts with other nerve cells that are downstream of it,” said Goulding, adding that the contacts these axons make are called synapses.
Describing the effect of the synapses, he said, “Dendrites [on an adjacent cell] have these receivers for those things called neurotransmitters “¦ when the neurotransmitter binds to this particular receptor “¦ it’s a chemical and it allows ions to pass through the membrane of the cell.”
Finally, after the ions pass through the membrane of the cell, the cell becomes either negatively or positively charged, depending on the type of ion passing through. Once the charge reaches a certain threshold, it will “fire” or create an action potential.
“It induces that cell to release the neurotransmitter that it has in an axon to the next cell in the chain “¦ you’ve got this chain reaction,” Goulding said regarding the signaling system.
Goulding’s brainchild, the notch pathway, is the mechanism that dictates whether an immature prototype will become an excitatory or inhibitory neuron. If these two types are not equally represented in the body, problems like epilepsy (too many excitatory neurons) or tetanus toxin (too many inhibitory neurons) occur. At some critical point during embryo development, an inventory must be taken to ensure that excitatory and inhibitory neurons are equally balanced.
The notch pathway provides a basic explanation for the sequence of steps that allows this inventory to happen in a tiny, undeveloped embryo. Goulding said that the notch pathway allows cells to talk to each other and figure out that half need to develop one way and half the other way.
Goulding likened the sensitivity of the notch pathway to the differentiation of two cells at the same postal address. It is much more difficult to discriminate between cells at the same postal address than cells separated from Solana Beach to Encinitas on a map, he said.
“What happens is, at some point as our brains develop, cells have the same postal address but they really need to do two different things.” Goulding explained.
Future research on this topic will prove or disprove the notch pathway as influential over more than just neuron type. It could, perhaps, control larger pathways, making this small step a foretaste of a much larger discovery. That answer is yet to be determined.