Even today, the brain still largely remains a mystery. For Silvia Arber, too. But precisely here lies the attraction for the internationally recognized Swiss neurobiologist: «Venturing into unknown terrain with the prospect of discovering something that no one has ever seen before, motivates me each day anew.»

Her fascination with the brain, her curiosity and open-minded approach are arguably also the key to Arber’s fundamental discoveries. With her team at both the Biozentrum of the University of Basel and the Friedrich Miescher Institute for Biomedical Research (FMI) she investigates how the nervous system controls the broad repertoire of simple to highly complex body movements. Her goal is to unravel the map of the neuronal circuits connecting the brain and the muscles and to decipher its function.

The brainstem – an important switchboard

Almost every activity of the brain results in a movement. Whether it is walking, talking, grasping or breathing, neurons always provide the impulse. The brainstem, acting as a switchboard, plays a major role in this process. From here, the instructions for when and how a movement is to be executed are transmitted to specialized executive circuits in the spinal cord. Motor neurons in the spinal cord then innervate muscle fibers causing them to contract. The organization of many of these motor circuits is similar in humans and animals. This is one reason why mice are suitable models in neurobiology to study the architecture and function of neuronal circuits.

Currently, Arber is particularly interested in neuronal circuits residing in the brainstem. «We want to understand,» says the neurobiologist, «which types of neurons are found there, their exact location, how they are connected to each other and which motor behaviors they coordinate.» Viral and optogenetic methods are being implemented to determine the identity of nerve cells, to visualize of the flow of information linking them, and to understand their function in behavior.

Neuronal subpopulations control specific movements

Using these methods, Arber has demonstrated that the brainstem comprises many subregions in which neurons with similar function reside. For example, there are neurons which control the speed of locomotion in the mouse and others control the forelimb reaching for food. For grasping a piece of food, yet another group of nerve cells is responsible. The various brainstem regions are connected to highly specialized, functionally distinct neuronal circuits in the spinal cord.  

«The brainstem coordinates diverse motor behaviors through its complex connectivity patterns,» says Arber. «Interesting was our discovery that there are more brainstem regions involved in the control of forelimb than hindlimb movements. This might be a reason why not only mice but also humans are more skilled with their hands than with their feet.» Complex movements, such as grasping with the fingers, require additional communication between brainstem neurons, before instructions are transmitted to circuits in the spinal cord for execution of the planned movement.

Understanding motor behavior disturbances

In her research, Arber’s primary focus is to unravel the neuronal circuits involved in motor behavior and to identify their functions. This work also has high clinical relevance. Understanding connectivity and function of circuits linking the brain to muscles will no doubt also help to delineate neuronal populations affected in nervous system disorders and spinal cord injury. This knowledge may prove important for treating diseases in which movement is impaired. «We first need to understand how the brain works before we can understand why it doesn’t work,» explains the neurobiologist.

As her fundamental findings could be important for future medical interventions, Silvia Arber was awarded the Louis-Jeantet Prize for Medicine in 2017 – one of many major awards. Since 2020, she is also a member of the National Academy of Sciences (NAS). Acceptance into the American science academy is considered to be one of the highest distinctions received by a researcher.