Life of PI: Searching for the mechanistic explanations of brain function

(Note: the PI, or principal investigator, is the research group leader)


Alfonso Renart, principal investigator of the Circuit Dynamics & Computation lab at the Champalimaud Centre for the Unknown, develops mathematical models to try to explain the mechanisms underlying cognition.

For most of his scientific career, Alfonso Renart has been working at the frontier between computational and experimental neuroscience, developing mathematical models that try to explain salient properties of the activity of neurons in cortical circuits and how these embody the computations that underlie cognition.

“My long-term interest is to understand the computations that underlie aspects of behavior associated with agency – that is, the ability to act freely to satisfy one’s goals”, he explains. “Studying the details of animal behavior allows us to understand and manipulate these computations, and thus to isolate the mechanisms relevant for a given task.”

Renart was born in Madrid in 1973, but spent the first five years of his life in California, where his scientific parents were both doing their postdocs at Stanford University – he in molecular biology, she in biochemistry. He started going to school upon his return to Madrid, the city where he remained until his early twenties. “I was a good student, I liked sports, I have good memories of those times”, he says.

He studied Physics at Madrid’s Universidad Autónoma from 1991 to 1996 – but, according to him, his family’s scientific background only influenced this choice implicitly. “I was good at math and physics, so I studied that”, says Renart. “I wasn’t thinking about making big decisions at the time, I just liked what I was doing and kept on doing it.”

He might have gone on and done his PhD in Physics had he not stumbled upon an ad for a PhD position, posted on a department wall by a researcher, Néstor Parga, who was studying how Physics relates to the brain. “I had a strong belief in the ability of physical theories to predict what will happen. But at the same time, physics had nothing substantial to say about how to predict behavior, nor are organisms fully unpredictable. Because organisms are nevertheless physical systems, it seemed like something fundamental was missing, and I was excited to get closer to this problem”, he recalls.

So Renart ended up doing his doctoral thesis at the intersection of Physics, Math and Neuroscience, specifically on mathematical models of associative memory, which are artificial neural networks “that store concepts and learn to recognize prototypical patterns”, as he explains. Just like the brain, he points out, these networks are able to categorize visual sensory inputs and recognize shapes as being letters, for instance, even when the images of the letters presented to the network are degraded.

“I chose neuroscience somewhat at random, but I soon realized I really liked it”, says Renart. But that wasn’t the only reason why his career suddenly took this unexpected turn. The thing is, he adds, Physics has become very technical, “so you spend a long time studying techniques and you need to be a real expert before you start developing insights on the problems themselves”. On the other hand, in neuroscience, “the problems are closer to us, and you can more quickly develop intuitions about the things you are studying. I liked this then and I still do today.”

Between 2000 and 2003, Renart did his postdoc at Brandeis University, in the US, on models of working memory. Working memory is the type of short-term memory that allows animals (and humans) to internally store and actively manipulate sensory information which is no longer present in the environment – like what we do when we transiently memorize a phone number we have just been told during a few seconds before we dial the number. Working memory, says Renart, is what frees us from the “immediacy of the environment” and allows us to develop an inner life, to mentally simulate the world.

In 2003, he returned to Spain to work as a junior principal investigator at the Institute of Neuroscience in Alicante. But he only remained there for a year, because by now he wanted to learn how to do experimental work, and not only theoretical modelling, and this ended up being difficult in Alicante. “I wanted to study real networks, to register the activity of many neurons – to experimentally study the same networks I had studied from the theoretical, mathematical, point of view”.

So from 2005 to 2010, Renart was back to being a postdoc in the US – this time at Rutgers University –, and doing experiments on the way rodents discriminate temporal intervals. “The perception of timing fascinates me, it is the primordial context in which everything else happens”, he says.

He arrived at the Champalimaud Centre for the Unknown (CCU) in early 2011. “I was looking for a job, I knew Zach Mainen by name and had heard about the Neuroscience Program here”, he recalls. “I came to visit for the first time in 2009 – there wasn’t even a building then – and I really liked the people I met. Also, Portugal is right next to Spain, and closer to the Mediterranean cultures than other places where I had applied”, he adds.

His group at the CCU – the Circuit Dynamics & Computation lab – now includes eight people (PhD students, post-docs, technicians) and is currently studying various problems – including the mechanisms underlying simple sensory decisions, the way that default behavioral strategies shape the optimal solution to experimental tasks, or the impact of the large-scale dynamics of the brain on sensory processing.

Asked to give a global perspective on his approach in neuroscience, Renart admits that while he enjoys and believes in the usefulness of finding mechanistic explanations of biological phenomena, he also feels that, in the process of relating animal behavior to the functioning of simple machine-like elements, sometimes it feels like something essential about biology inadvertently escaped. “I feel like I’m still very much searching for a way to describe the essence of what it means to be a living organism in purely physical terms”.



Ana Gerschenfeld works as a Science Writer at the Science Communication Office at the Champalimaud Neuroscience Programme



Edited by: Catarina Ramos(Science Communication office). Photo credit: CCU


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