The vast majority of people with autism experience unusual phenomena relating to some or all of their senses. For example, they may find contact with some materials to be unbearable. Andreas Frick, Inserm Research Director at Neurocentre Magendie in Bordeaux, is trying to understand the neural dysfunction behind this atypical perception in order to propose treatments. In 2019, his work was awarded the Marcel Dassault Prize by the FondaMental foundation.
Most well-known among the Autism Spectrum Disorders (ASD) are social cognition impairment, repetitive behaviors, and restricted interests. But a large majority of people with autism – 85 to 90% according to the studies – also have atypical perception of sensory stimuli: sights, sounds, touch, tastes, and smells. In 2013, these sensory alterations were included among the criteria for defining ASD – improving how these disorders are diagnosed and managed. One researcher working to improve knowledge in this area is Andreas Frick, based at Neurocentre Magendie* in Bordeaux. In 2019, his work was awarded the Marcel Dassault Prize by the FondaMental foundation, in recognition of an approach that he summarizes as "understanding neural function to help elucidate the clinical alterations observed in psychiatric diseases".
Combining basic and applied research has undeniably been the leitmotif of the neuroscientific career of the German-born researcher. A choice that was not immediately obvious. "After high school, I hesitated between studying art, architecture, and biology, he explains. In the end I opted for marine biology, followed by the neurosciences."
From understanding basic neural function…
During his master’s and dissertation at the Max Planck Institute of Psychiatry in Munich, he "first wanted to understand the very basic functioning of the neurons and how they process information in the neocortex. This outer layer of the hemispheres, which represents almost 70% of the brain, is implicated in memory, motor control, language, and the processing of sensory information," he explains. In 1999, for his postdoc, he joined the team of Daniel Johnston, a specialist in the processing and storage of information in the neurons, at Baylor College of Medicine in Houston, USA. There he continued to study pyramidal neurons, a specific population of cortical neurons named after their pyramid-shaped cell body, capable of adapting to stimuli. He was particularly interested in the plasticity of their excitability, which can hinder the processing and storage of information. "It was a very enriching experience, not just scientifically but also personally because the area was home to an intense international artistic scene. During this period I also had the opportunity to go to the Woods Hole Marine Biological Laboratory where I was able to develop collaborations – notably with Jeffrey Magee at the neuroscience center of New Orleans, remembers the researcher. My five years in the States were great and I could have stayed on as assistant professor at the University of North Carolina at Chapel Hill. But for social and cultural reasons I preferred to return to Germany. I continued to remain very European."
In 2004, he joined the Max Planck Institute for Medical Research in Heidelberg where he founded his own research group within the Cell Physiology laboratory headed by Bert Sakmann, one of the recipients of the 1991 Nobel Prize in Physiology or Medicine. "I was convinced that basic research, particularly into sensory processing, could shed light on neurological and psychiatric diseases, emphasizes Frick. Thanks to Bert Sakmann, I was able to study the neocortical microcircuits involved in sensory information processing. That was also the opportunity to start working on a mouse model of fragile X syndrome, which is a common cause of autism. However, after three years, I wasn’t seeing any interesting opportunities in Germany, so I looked for other options in the UK, Switzerland and France." That was when Giovani Marsicano, whom Frick had known at the Max-Planck Institute in Munich, told him about Neurocentre Magendie in Bordeaux that he himself had just joined.
… to that of sensory information processing in autism
Upon meeting with its Director, Pier-Vincenzo Piazza (Inserm Grand Prize 2015), Frick was convinced that Neurocentre Magendie would be a good fit. "I found the newly-established [in 2007 ed.] institute to have a lot to offer. It had international teams of an excellent caliber and was renowned in Europe. What is more, Inserm’s culture promotes clinical applications." Thus in 2008, thanks to Inserm Avenir funding, he set up his own team there. A year later, he was promoted to Research Officer following a competitive examination. Since 2016, he has held the role of Research Director, leading the Mechanisms of Cortical Plasticity in Normal and Pathological Conditions team. The neural circuits of the neocortex have remained central to his work, but according to two clinically-related orientations. He is studying the mechanisms of memory formation and the processing of sensory information in autism. "In 2014, we used a mouse model of fragile X syndrome to show that tactile hypersensitivity is linked to a dysfunction of channels through which ions pass at neural level, specifies the researcher. It turns out that the tactile sensory systems of the mouse paw and human hand are 90 to 95% similar. The mechanism discovered in mice could therefore be a potentially useful therapeutic target for people with autism."
At present, it is this proximity between mice and humans that he wishes to make broader use of. "We are looking to define behavioral tasks comparable between the two species that induce atypical perceptions. Then, using various tools such as imaging and electrophysiology, we will study what happens in the area of the neocortex that processes this sensory information. The objective is to obtain signatures that are characteristic of atypical processing. Finally, thanks to the mice, we will be able to observe what happens at cell level, define therapeutic targets, and test pharmacological treatments that could in time help people with autism, describes Frick. The Marcel-Dassault prize has been a major help. In addition to recognizing our approach, it enables us to hire a postdoc, add to our equipment and above all facilitate collaboration with medical doctors through FondaMental."
There is no doubt that twelve years after arriving in Bordeaux, the German researcher does not regret his decision. Same for his wife and co-worker, Melanie Ginger, and their two daughters aged 11 and 14. "They have integrated very well and, even if I don’t have much time, Bordeaux enables me to climb, ski, and enjoy the sea, he acknowledges. So moving again is out of the question!”
*unit 1215 Inserm/Université de Bordeaux