Our brains are made up of billions of tiny cells called neurons, which communicate using electrical impulses. When neurons connect, they do so at a specialized point called a synapse. Synapses are essential for processing everything we experience—sensation, perception, and thought.
The most well-known type of synapse is the chemical synapse, where chemicals known as neurotransmitters, like dopamine and serotonin, are sent through small bubble-like structures. However, there’s another lesser-known type of synapse called an electrical synapse. Although these form about 20% of all synapses in the brain, we still don’t know much about which molecules are used to create them.
William Crow, a third-year ARCS scholar, is exploring this very question.
“My work is exploring the basic principles of how these electrical synapses are built. It is cool because we know so much about how chemical synapses are made – but we are just beginning to scratch the surface on what we know about electrical synapses” says Crow.
To investigate how electrical synapses develop, Crow is using zebrafish as a model organism. These small, tropical fish share key similarities with humans, including genetics and the presence of electrical synapses in their brains.
To identify the molecules involved in forming electrical synapses, Crow and the rest of the Miller lab are using a cutting-edge technique. It works similarly to how security tags function in clothing stores: when someone tries to tamper with the tag, it sprays dye, marking anything nearby. In the lab, instead of dye, they use a molecule called biotin, which "labels" nearby proteins at the electrical synapse. This is the first time this approach has been used to identify molecules at electrical synapses, generating a long list of potential building blocks.
Crow is now working through this list using various techniques to identify which molecules are essential for electrical synapse function. One approach involves removing specific molecules to see if the electrical synapses are affected. So far, Crow has discovered seven previously unknown molecules that play a role in the formation and function of these synapses. His research is shedding light on the intricate processes involved in building electrical synapses, offering new insights into how our brains communicate at a fundamental level.
“I am really excited that we have been able to identify new molecules that are important to the electrical synapses – not only because it begins to help us understand a parts list for these synapses, but because it also may provide a link into different conditions like epilepsy or autism,” says Crow.
While there’s still much to uncover, Crow’s research is already starting to clarify the role electrical synapses play in brain function and neurological conditions. By identifying the key molecules involved in building and maintaining these synapses, his work is not only helping to create a "parts list" for these structures but also revealing how disruptions in these components may contribute to developmental disorders like epilepsy and autism. Understanding these molecular mechanisms is crucial, as it brings us closer to decoding how the brain communicates at a fundamental level. With the support of the ARCS Foundation, Crow’s work is uncovering new pathways that could explain how electrical synapse dysfunction contributes to neurological disorders, offering potential targets for future therapies.
