Lisa Genzel's work at the Translational Neuroscience Unit

It's key that the animals are kept calm and relaxed

Lisa Genzel

Associate professor, Donders Institute

Lisa Genzel is an associate professor at the Donders Institute. She conducts research into the memory processes of mice, rats and humans. In this interview, she explains why animals are essential to her research, and how she ensures they are handled responsibly.

What do you research at the Translational Neuroscience Unit?

My research is focused on understanding how we go from individual experiences to broader knowledge. If you ask someone what the capital of France is, for example, they’ll know it’s Paris, but they don’t know how they know what. I want to know what happens in the brain when we try to think through something like this.

For that, I work with different research subjects: humans, rats and mice. We study their behavior during various complex behavioral tasks. One of our main tools is the HexMaze, which is a large spatial maze that the subjects need to navigate through. For rats, the maze is 5 by 9 meters; for mice, it’s 2 by 2 meters. For humans, we’re working with a virtual reality maze that feels akin to roughly the size of a football field.

Why do you use these three different species in your research?

Depending on the research question we’re investigating, the method changes. And when the method changes, the species changes. We use mice for molecular techniques, to visualize memory traces. Rats are used for electrophysiology, which involves recording their neuron activity. Both of these techniques are invasive and that’s why not possible in healthy humans. Instead, with humans, we can use MRI-scanning to observe whole-brain learning over time.

Ideally, I would do all my experiments with humans, but that is not possible. The good news for me is that the brain areas and mechanisms involved in such memories, are the evolutionary conserved in mammals. That means I can use rats and mice to understand the detailed mechanisms which I cannot query in humans since the same things happen in their brain as in ours.

Mice participating in animal research, exploring a hex maze

Why is it essential for you to use animals in this research?

I actually started my research in humans – throughout my PhD research, I only worked with human subjects. And then, later on, I switched to rodents because some questions just can’t be answered with humans. That’s because the hippocampus, one of the main brain areas that’s crucial for memory, is buried really, really deeply in the brain. The only way to access that, if I want to record anything, is to implant something.

In my lab we implant electrode into the hippocampus under anesthesia. This allows us to record the activity of individual cells in the brain both during learning and sleep, We believe, but still have to prove, that new memories are replayed during sleep, this allows your brain to pull out of the facts from every experience that are important and you want to keep for a long time in your memory storage. And for that, I have to move to a rodent. Then, the molecular methods that lets us identify which cells are part of the memory trace, those require taking the brains out, which is also not possible with humans.

How do you ensure those animals are handled safely?

As a memory researcher, I want to understand healthy physiology. I don’t research stress, so if the animals I was researching were stressed it would change the whole experiment and make results meaningless. That’s why it’s key the animals are kept calm and relaxed.

Our main approach in this is to play a lot with the animals. We ensure that they like us, that there’s frequent positive interactions, and that any behavioral tasks that are done are natural to the animal. We try to avoid any reinforcement, and if there is any, it’s always positive, so that the subjects stay close to their natural behavior.

In our lab, there’s multiple people handling animals. Before anyone gets to handle them, they go through me. Only if I’m certain the animals are handled with respect, are you allowed to start the research. We also developed some videos on how to handle them with care, which is similar to how you handle your pet or a child. Anything that might make the animal unhappy, we avoid.

Mice participating in animal research, sniffing at a small bottle

How do you look at the concept of animal-free innovations?

We use humans and computational models when possible. But cells in a dish can’t form memories or solve mazes. Even if we built a system that could, its cognitive complexity would mean it deserves protection like an animal. The level of cognition we study requires sentient models.

Some people say animal research should only be allowed if it is directly related to curing diseases. What’s your view on this?

I occupy myself with fundamental research. That’s research where we can’t always predict the impact in advance, but it often leads to major breakthroughs. Think of the moon missions by NASA, for example. Landing on the moon isn’t by itself useful for humanity, but the research by NASA has given us so many other benefits: from better weather predictions to safer firefighting equipment to various medical technologies.

We want to understand how the brain solves complex issues. That can help us build better artificial intelligence solutions, for example. If we can model AI systems on the brains of mammals, it might vastly improve them.

And on the medical side, there’s mental health diseases. Take depression. It’s currently defined by symptoms but likely includes many distinct disorders. Some new theories suggest it’s a memory disorder—people get stuck with the wrong memories. New antidepressants like ketamine may work by erasing or altering memory. To understand that, we first need to understand how memory works.