Mixed synapses
These mixed synapses remain largely unexplored. “They have been described in animal models, but never in humans,” says Scheefhals. “Thanks to advanced cell models, this is now possible: we can turn skin cells into stem cells, which are then developed into nerve cells. This has allowed me to show, for the first time, that mixed synapses also exist in human nerve cells. What exactly they do, we still don’t know. That makes it so exciting: they could play a key role in the development and flexibility of the brain.”
Her research thus touches on a broader question: why is human brain development so slow? "In mice, maturation of synapses takes weeks to several months, while in humans it takes about 20 to 25 years. This prolonged development makes us unique, giving us flexibility and learning ability, but it also makes us vulnerable. It increases the chance that the delicate balance between “accelerator” and “brake” can go wrong, precisely what we see in developmental disorders such as autism."
From mix to match
“I believe mixed synapses are a transitional stage that can develop into fully functional synapses. This transition may be an important mechanism for maintaining balance in the brain during the long period of maturation humans experience.” Scheefhals uses a metaphor to explain this: "Imagine a synapse as a caller and receiver in a telephone conversation. Normally, both speak the same language: that is a “match”. In mixed synapses, however, they speak different languages: a “mix”. An important connection has been made, but there is no real communication yet. However, if needed, contact can be established – with someone else who does speak the language taking over the conversation. This creates a “match” again, allowing the message to be passed on. This transition from mix to match may play a crucial role in the flexibility of the brain. Whether it works exactly like this remains to be seen, and that is precisely what I aim to investigate."
New techniques, new opportunities
Thanks to technological advances, such as the new microscope called microSCOOP (where “scoop” stands for “scooping”), Scheefhals can effectively “scoop” specific synapses out of nerve cells and study them in detail. This allows her to investigate which building blocks are present in mixed synapses and how they change during development. “Every time I look through the microscope, I feel the excitement and curiosity that drives my research,” she says.
The ultimate goal is not just fundamental understanding, Scheefhals emphasizes: 'If we learn how the flexibility of synapses works, we may also be able to intervene when things go wrong. Mixed synapses then offer new starting points for treatments for autism and other developmental disorders.'
Or, as she herself says: ‘For me, it's about fundamentally unravelling how the brain works. But ultimately, I hope this can help patients. That's what gives the research meaning.’
