Synergy Grant 2025: Zoltán Nusser, Attila Losonczy, Ivo Spiegel

This huge grant success fits in very well with Zoltán Nusser's achievements and awards to date, and perhaps even more so with the short text intended to whet the appetite, which can be read on the ERC website announcing the Synergy grant: Are you a researcher who wants to tackle an ambitious research problem that you cannot solve with your team? Synergy Grants may be for you!"

We learned how the winning trio started writing their application and what the topic of the application is:

"I had a PhD student, Attila Losonczi, who, after Columbia University,  founded a lab in Texas (Univ. of Texas Southwestern Medical Center). We met two years ago at the KOKI Days, and that's where we started talking about what kind of joint project we could do.

The deadline for this Synergy grant application was last November, and we started thinking about what should be our main question and what experiments should we use to investigate it. Attila has a collaborative project with Ivo Spiegel, and at his suggestion, he became the third member.

The Synergy Grant is open to teams of two to four leading researchers working together to solve ambitious research problems. The basis of this grant is the synergy indicated in its name, which must develop between the research teams. Everyone must contribute technical knowledge that reinforces and interacts with each other.

In our case, this involves molecular sequencing, genomic-bioinformatical methods based on the knowledge of Israeli professor, Attila Losonczi will conduct in vivo experiments – in vivo imaging/imaging behavioral experiments, and my part will be to connect the two parts – to bridge the cellular and molecular parts.

It took quite a long time to put together a concept that all three of us could feel was our own, and we are investigating a question of such significance that we have a chance of convincing the ERC decision-makers that the three of us can achieve important progress in this area.

The aim of the proposal submitted under the name MemoryLoci is to understand the remarkable learning and memory abilities of the mammalian brain.

The program itself, the project, is to explore the cellular, subcellular, synaptic, and molecular mechanisms of hippocampal spatial memory formation. We plan to achieve this through combined in vivo behavioral imaging, followed by in vitro electrophysiological measurements, morphological, ultrastructural, and molecular characterizations, and genomic characterization of these cells.  We examine spatial memory in virtual reality, in animals navigating in space."

- What is the working hypothesis?

- Our hypothesis is more or less that different types of cells are involved in the formation of a memory trace, which have different molecular compositions, express different genes, and will change their own activity during learning through different molecular-cellular mechanisms.

One of the main questions would be to determine what types of long-term synaptic plasticity processes will occur and what molecules will play a role in different cell populations.

- Which area of the brain will you be studying?

The area under study is the CA1 region of the mouse hippocampus, and we will be studying the CA1 pyramidal cells.

In these CA1 pyramidal cells, we will look at what functionally definable cells are involved in behavior - navigation - learning. It has been known that there are cells that are only active in certain places, such as the reward zone, where the animal receives a reward; there are cells that are active everywhere in different environments, no matter what context humans put them in, and there are those that are specifically active only at certain points in space. Some cells change their activity from day to day, while others show relatively constant activity. There are some usually "silent," they are known as silent cells.

We believe that the gene expression profiles of these cells are also different. And if we uncover these differences, then these differences in gene expression will give us the tools to first create viruses then create transgenic animals in which we will try to influence these specific CA1 subpopulations (subgroups) and try to decipher their effect on learning, spatial orientation, and spatial memory.

-  The application had to be submitted last fall. What happened after that?

- Synergy is a three-round competition. After successfully passing the first and second rounds, we made it to the third round, which was an interview where we had to present the application in person; the three applicants had to present the work together. This third round took place in Brussels. In order to prepare thoroughly, we went to war-torn Israel and spent a few days there, but the main thing was that we put together a presentation, which we then rehearsed several times in front of our knowledgeable colleagues at the Weizmann Institute.

- Ivo Spiegel works at Weizmann, which is ranked sixth on the list of the world's best institutes this year, but the timing could have been better. What was the third factor?

 - There are experts who were not only specialists in the field, but whom we could also trust to give us their honest opinion. It was very important that the presentation in Brussels be a great success. This three-part presentation had to flow smoothly, with each part connecting to the next – and we worked hard on this.

All three of us felt it was important to be able to convincingly demonstrate that we genuinely believe in the experiments included in the application, that we really want to do them, and that we didn't just get together to raise money so that everyone could do their own little thing, and then collaborate on something from time to time, but that everyone contributes their own knowledge, and thus the result will truly be greater than if we worked separately.  That is the essence of the entire application.

- I hope that everything goes as well as possible! What is the expected result?

- If we can do everything as planned, we will have a new concept for the formation and long-term storage of memory processes. This does not necessarily mean that no one has ever thought of anything similar, as there are many different hypotheses circulating in the world, but hopefully we will have solid, unshakeable evidence for this concept!

- What can be achieved with this in practice?

I wouldn't go so far as to say that this will help us determine, for example, when and why people with Alzheimer's experience memory loss. But once we have completed the experiments we have just outlined, there are various possibilities for continuing the research.

One is to see if what we found here also applies to other types of memory that are not dependent on the hippocampus. One example would be to examine cortical representation memory to see if we can also see different functional subclasses there and, within them, other molecular mechanisms for the development of synaptic plasticity processes. If this is also the case there, then it would be possible to generalize more, and the whole thing would not be specific to the hippocampus – but we don't know that yet.

- And if you don't find that?

- You can't do science without a hypothesis! But even if our hypothesis is not proven by our own experiments, but rejected, we will still be just as happy, because it is just as important for us to know that cortical processes are different as it is to know that they are similar!

- I see. Let's say we already know about this very important issue in mice. And where do humans come in?

- If we've looked at rodents, we can look at primates, and if we get similar results there, then there's a good chance that it's the same in humans.

- Could you give me an example of how this knowledge, acquired through enormous effort, can help?

- In human studies, the question arises: if plasticity processes involving different mechanisms play a role in different cell types involved in memory formation, is there a disease in which one or all of them malfunction selectively? Will there be a similar degree of degradation in cells that encode a specific event or different cell types are affected to varying degrees?  When we find these mechanisms in the cells responsible for encoding normal memory processes in control mice, we can examine these phenomena in animal models of various diseases and determine which cells and which mechanisms are damaged.

 - Did you talk about this in Brussels?

- No. Translation, the applicability of the results to humans, is not part of this ERC grant. In order to be in the top 10%, we had to convince the panel that we were there in terms of ideas, preparedness, and synergy. We succeeded.