Since its start in January 2021, a consortium of UZH research groups in the University Research Priority Program (URPP) “Adaptive Brain Circuits in Development and Learning” (AdaBD) has been working on unraveling the complexities of brain adaptability and its role in development and learning. This interdisciplinary program, spanning diverse fields from molecular neurobiology to whole-brain dynamics, aims to bridge basic research with clinical applications in order to better understand dysfunctions that lead to developmental delay and learning disabilities. As the program reaches its halfway mark, Fritjof Helmchen from Brain Research Institute, University of Zurich, co-director of the URPP AdaBD together with Esther Stoeckli, shares insights into its goals, achievements, and future directions.
Hi Fritjof, you are part of this research program investigating the biological basis of learning. What exactly are the main goals of this program?
All brains form during development and continue to change throughout life, especially when animals or humans learn something new. We aim to discover what changes occur in brain circuits, how their activity patterns adapt, and how these changes relate to behavioral improvements, such as enhanced performance in specific tasks. Additionally, we seek to understand the neural deficits that contribute to learning impairments and find ways to improve the diagnosis of such conditions and the support of affected people.
A total of currently 19 groups from the University and University Hospital of Zürich are involved in the program – how was it founded in the beginning?
The program was founded based on discussions within the Neuroscience Center Zurich (ZNZ) that identified brain adaptability as a common topic of high interest across the different institutions. Esther Stoeckli and Martin Müller from the Department of Molecular Life Sciences, along with myself, took the lead in bringing together groups from four faculties with very diverse backgrounds and expertise. In our concept, we proposed projects spanning several dimensions (from genes to circuits to behavior; from animals to humans and back). We also identified multi-sensory learning, i.e., how the brain integrates its diverse sensory inputs, as a central shared research topic.
What are the program’s main impacts on society?
Our program primarily aims to generate new scientific knowledge, as we still know relatively little about the mechanisms underlying brain adaptations. Our network includes clinical groups that assess and treat children with developmental delays or learning disabilities (e.g., difficulties with reading, writing, or math). Through our work, we hope to develop improved diagnostic procedures to identify and stratify these children. In the long run, a better understanding of normal brain adaptations and the potential disruptions in these processes may inspire new treatment options.
What was your personal motivation to get involved in the program?
My research interests have always focused on understanding how neural circuits function and how they guide behavior. For a good decade, new methods have made it possible to track the activity of the exact same neuronal populations in the mouse brain over weeks and months. These advances have opened the door to more comprehensively study long-term brain changes, particularly those occurring during learning. Our program allows me to link our findings to research on the human brain, and I am excited by the prospect of uncovering core principles of brain adaptability.
The program has now reached the halfway point. What were the main achievements until now?
Since 2021, we initiated 18 collaborative projects that connect the URPP groups and leverage their synergies. We also established several platform services to support our network in areas such as data acquisition, model systems, and data analysis. Our microscopy platform has been particularly successful and is widely used by many groups. This year, we have established a new platform focused on increasing knowledge and awareness of learning disorders. This platform fosters collaborations within our network and has a strong focus on the transfer of knowledge to society. Additionally, as consortium we actively promoted networking and career development through various events and participated in several public outreach initiatives.
What were the biggest challenges and difficulties you faced so far?
Bridging research efforts between basic sciences and clinically oriented research remains challenging, as they typically operate at opposite ends of the relevant spectrum (animal models vs. humans, molecules/cells vs. whole brain/behavior). We aim to close this gap with several approaches: we apply human tissue models (partly derived from patient saliva), we establish analogous experimental approaches in both animal and human studies, and we develop computational models that connect the different scales.
Can you give us a short outlook on the future of the program – what are you most looking forward to?
In the second phase, the URPP AdaBD will refine its research plan by strengthening some ongoing projects and introducing new topics. We will place a particular emphasis on promoting translational projects to bridge the gap between basic research and clinical applications. Additionally, we will consolidate and expand our platforms, with a major goal of securing long-term funding to ensure the continuation of the URPP beyond 2028. This is not possible without human power, which is why we will be advertising some interesting new job positions over the next few weeks.
Anything else about the program or the people involved you would like to share with us?
Working in such an interdisciplinary consortium, where everyone is exposed to very different viewpoints, has been both rewarding and productive. It fosters a positive environment where everyone can learn extensively, critically assess their own approaches, and be inspired to generate new ideas. I have thus far enjoyed it a lot.
Thank you and all the best for your research!
Useful links:
General program website: www.adabd.uzh.ch/en.html
Website of URPP AdaBD Microscopy Platform: https://www.mesospim.org
Website of Learning and Learning Disorders (LLD) Platform: www.lld.uzh.ch (in German)
UZH News:
www.news.uzh.ch/de/articles/2021/lernen.html (in German)
www.news.uzh.ch/de/articles/news/2023/brainfair23.html (in German)
Images:
Josh Applegate, Unsplash