Understanding Brain Development and Learning

The new University Research Priority Program (URPP) “Adaptive Brain Circuits in Development and Learning” aims at better understanding the mechanisms underlying brain development and learning as well as the causes of learning deficits. The URPP just received its go and will start in January 2021. With the URPPs, the UZH is opening new avenues for innovative research in areas relevant to our society. We talked with Esther Stoeckli (Department of Molecular Life Sciences) and Fritjof Helmchen (Brain Research Institute) about their plans for their URPP.

ZNZ News: What are the aims of this URPP?
Fritjof Helmchen: Learning new behaviors is essential for us as individuals, both during childhood and as adults. Therefore, if there are deficits in learning, especially during development, it can have a large impact on the affected individuals, their families, and society. Learning requires specific adaptations in neural circuit structure and function. The aim of our URPP is to advance our understanding of the cellular and molecular mechanisms that are involved in brain circuit development and in learning-induced changes. Using innovative methods and a multi-disciplinary approach, we want to connect the molecular and the systems level. We also want to translate between animal models and humans, with the goal to identify which brain circuits are essential for facilitating multisensory learning in children and adults. These scientific insights will help us to generate tools for improved diagnosis and eventually promote treatment of neurodevelopmental disorders and developmental delay.

What triggered the start of the URPP?
Esther Stoeckli: Over the last years, more and more research groups at UZH became interested in brain circuit development and brain mechanisms of learning. In addition, new methods have now become available that allow more detailed studies than ever before. In part, the URPP was triggered by the development of a new microscope in the group of Fritjof, which enables high-resolution 3D views of entire developing nervous systems (see mesospim.org). This application ignited collaborations with my group and several other groups. At the same time, closer interactions among basic researchers and clinical scientists started to develop due to their joint interests in the role of specific genes and molecules in brain development. In this way, a new network of collaborations started to surface exactly at the time when the Call for new UZH URPPs was published. A welcomed coincidence!    

What does the research plan look like at a high level?
Fritjof Helmchen: Our research plan is divided into three major subprojects reflecting the core goals of the URPP. First, we will work from the bottom up, focusing on the molecular and cellular mechanisms of how neural circuits are established (or fail to form correctly), starting from specific genes identified as key candidates. In a second, complementary approach, we will use a top down approach, starting from learning behavior in juvenile and adult animals and humans, with the aim to pinpoint core circuit components, e.g. cell types that adapt their functional properties and thereby contribute to learning. And our third path of investigation will be to translate the results of these studies to human brain circuits. Here we want to develop specific tests for children with developmental delay that will help to improve diagnosis. Our URPP connects to a large cohort of such children and hopefully at some point, we will be able to use our knowledge for novel therapeutic interventions.

What do you hope to achieve within the scope of the URPP?
Esther Stoeckli: We firmly believe that gaining deeper insight into the fundamental mechanisms of neural circuit adaptations is essential to also in the end devise new approaches for interventions in patients with impaired  learning abilities, such as for example in certain neurodevelopmental disorders. Therefore, the basic science, utilizing the great opportunities provided by new methodologies in both animal and human research, will be at the heart of the URPP and gaining mechanistic insights into the principles of neural circuit formation and adaptation is a foremost goal. On this foundation, the second major scope is the direct link of our URPP to a cohort of children who show developmental delay and learning impairments. This cohort on the one hand can provide us with hints about the genetic modifications causing these conditions, which will fuel basic research. On the other hand, we will be able to immediately and thoroughly assess new ideas for improved diagnostic tests and better stratification of affected children in a relevant cohort.  In view of the fact that about 2000 children are diagnosed with developmental delay in the Canton of Zurich alone, this is a very important question that is relevant to our society.

More information about the University Research Priority Programs

Image: Fluorescence microscope image of the nervous system of a developing chicken embryo (neurofilament staining visualized with a mesoSPIM microscope; courtesy of Fabian Voigt and Martina Schättin; Helmchen & Stoeckli labs)