Interview with Angelo Forli, coordinator of the IIT Neural Networks for Natural Intelligence Research Line
Starting from an interest in complex systems, Angelo Forli, trained as a physicist, specialized in neurobiology and went on to study the brain, with a particular focus on spatial and social memory functions in the hippocampus. After six years at the University of California, Berkeley, he chose to return to Italy, where, supported by several prestigious grants, he established a research lab at IIT. The lab focuses on two main directions: understanding the neural mechanisms that enable the brain to generate flexible behavior, with particular attention to hippocampal circuits, and investigating regenerative intelligence. This latter field, still very new, aims to uncover how the nervous system reorganizes during regeneration, drawing on the remarkable ability of some organisms to rebuild complex tissues and even entire organs.
«You have to bite into problems: I always tell the students in my lab this. It means staying with a problem and not letting go until it’s solved».
At the core of research, then, lies persistence. This is how Angelo Forli – coordinator of the Neural Networks for Natural Intelligence lab at IIT in Genoa – describes what he sees as a defining trait of scientific work. His lab was launched thanks to several prestigious grants, including one from the Armenise Harvard Foundation, which enabled his return to Italy in 2025 after six years at UC Berkeley; a grant from the Italian Science Fund (FIS) promoted by the Ministry of University and Research; and a recent award from the Human Frontier Science Program, which will support particularly innovative research in the neurobiology of regeneration.
But why “bite into a problem”? Because, as Forli explains, the essence of a researcher’s daily work is precisely this: identifying a problem and striving to solve it.
«You have to design an experiment, that is, create a controlled setting in which you can probe the system – here, the nervous system – and obtain answers. Often this requires developing dedicated tools that are not available off the shelf, combining hands-on skills with a good deal of creativity. And then, until the experiment works – or at least a simplified version of it does – I don’t let go. I keep trying, over and over. This is something I’ve seen in every successful scientist I’ve met».
Persistence, then, but also curiosity. These, according to Forli, are the key qualities of a researcher. He began cultivating them early on, as a child, when he would take apart alarm clocks and radios to understand how they worked. Or, as he once recounted in an interview with Corriere della Sera, when he experimented with making gunpowder in his basement («It’s very simple – you start from a pencil,» he says with a smile, while reassuring us that he never caused any explosions).
And there is one more essential quality, courage: «To do innovative research, you also need a certain degree of courage – almost a touch of recklessness – especially when opening up new fields. You never know where your experiments will lead. Often into a dead end – and then you have to start again».
After completing high school, Forli enrolled in Physics at the University of Padua, earning his bachelor’s degree with a thesis on complex systems and his master’s degree with research focused on neurons.
«As a physicist, I’ve always been fascinated by complex systems: systems made up of many units that, taken individually, may behave in simple ways, but through their interactions give rise to rich, surprising, and often hard–to–explain phenomena. It’s also the field that led to Giorgio Parisi’s Nobel Prize in Physics».
What led you from this area to neuroscience?
«The nervous system is perhaps the most emblematic example of a complex system. The brain, after all, is essentially a collection of neurons – simplifying somewhat. We have fairly solid theories about how individual neurons work. The challenge is the complexity that emerges when you start putting them together – three, four, five… all the way up to the roughly 90 billion neurons in the human brain. And it’s precisely from their interactions that thought, emotions, memory, the ability to play an instrument or conduct an orchestra emerge. In many ways, neuroscience is still at an early stage of understanding. For someone drawn to research, the appeal of the unexplored is irresistible.»
Where did you start, specifically?
«After completing my PhD in neuroscience and neurotechnology at IIT, I moved to Berkeley. At IIT, I had developed optical methods to interact with neurons and precisely measure their activity, but I felt something was missing: behavior, which is ultimately one of the brain’s primary outputs. So at Berkeley I began studying the relationship between neural activity and behavior, using animal models in environments as natural as possible. It’s one of the few places in the world where the neural basis of natural behavior is studied. I focused in particular on spatial and social memory, which are linked to the hippocampus, a brain region also extensively studied because of its involvement in Alzheimer’s disease. During my postdoc, I investigated how hippocampal activity responds to the presence of different individuals in a social context and, together with colleagues, studied the mechanisms of ‘replay’, a phenomenon in which the brain replays daytime experiences during sleep, often at accelerated speed and in reverse order. This phenomenon had mainly been observed in rodents; we showed for the first time that it is more widespread than previously thought, demonstrating its presence in other species as well. This opens up the possibility that it reflects an even more universal principle, likely present in humans too».
After returning to Italy, did you continue working on the hippocampus?
«Yes, focusing on a specific aspect: flexibility. While the hippocampus is traditionally studied for its role in spatial memory, it is now clear that it is involved in many other functions. We study how it becomes active in different contexts, especially those that require flexibility – the brain’s ability to adapt to very different tasks and situations – and try to understand the neural dynamics and mechanisms underlying this process. This led to a second research line, in a more frontier area, concerning what is essentially an extreme form of flexibility: regeneration. In particular, we study what we call regenerative intelligence, the ability of the nervous system to reorganize itself when tissues regenerate, restoring function. This remains a largely unexplored field, despite its importance».
Is this phenomenon limited to animals, or does it occur in humans as well?
«Humans do have some capacity for tissue regeneration, although more limited; for example, we can regenerate liver tissue, bone, skin, and, especially in childhood, even more complex structures such as fingertips. There are also regions in the brain, like the hippocampus, where new neurons continue to form throughout life, a process known as neurogenesis. In the animal kingdom, however, these abilities go much further. Lizards can regrow their tails; salamanders can rebuild entire limbs and complex organs, including eyes and parts of the brain; many invertebrates can regenerate large portions of their bodies; and even a small rodent, the spiny mouse, is capable of repairing tissue with surprising effectiveness, including the spinal cord. Much of current research focuses on the cellular and molecular mechanisms that make regeneration possible, with the long–term goal of translating them to humans. But rebuilding tissue is not enough: the real challenge is restoring function. The deeper question is: how do neurons reorganize to reconstruct functional networks capable of generating behavior again? This is still a very young field, technically challenging, but one that we believe can reveal fundamental principles».
Are there potential practical applications, in medicine or elsewhere?
«At the moment, our work is basic research, I wouldn’t say we’re close to direct applications yet. But in the future, the implications could be significant. Imagine being able to reconstruct parts of the body: in some respects, this is not so far off: prosthetics and stem cell therapies are advancing rapidly in regenerative medicine. At that point, understanding how to restore function after structural regeneration becomes crucial, and that’s where regenerative intelligence comes in. There are also potential implications for artificial intelligence».
Meaning applying brain–inspired mechanisms to AI?
«Exactly. There are countless examples of artificial intelligence drawing inspiration from neuroscience. It’s quite possible that by studying the neural mechanisms underlying flexibility or regeneration, we may discover principles useful for AI, for instance, algorithms that allow software or robots to repair themselves, or strategies to improve the interaction between prosthetic devices and the nervous system, or to develop intelligent agents that can adapt more flexibly to different contexts».
