Redesigning brain circuit

Rüdiger Klein receives an ERC Advanced Grant to analyze the development of amygdala circuits

March 31, 2020

The amygdala is important for the emotional evaluation of situations or objects. Aided by the amygdala, we are able learn to treat something with affection or aversion. How the amygdala controls the various behavioral reactions and which other brain regions are involved, remains unclear. In order to fill this gap in our knowledge, Rüdiger Klein attempts to specifically reorganize the development of the amygdala circuits in mice, thereby transforming innate and learned emotional behavior. The European Research Council (ERC) is funding this innovative project with a 2.5 million Euro grant over the next five years.

Circuits in the amygdala determine whether a situation is rewarding (such as when receiving food, left panel) or scary (like great heights, right panel). By manipulating these circuits, Rüdiger Klein hopes to gain insights into their development and function.

Fear protects us from danger, but can also stand in our way when it becomes irrational. A good feeling from eating encourages us to choose suitable food, but can also contribute to eating disorders. No matter whether it is fear, pleasure or other emotions, neurons in the amygdala link our feelings with internal and external stimuli and thereby control our unconscious behavior.

The information leading to rewarding or defensive behaviors is routed over different circuits within the amygdala. However little is known of how these circuits develop. Rüdiger Klein, Director at the Max Planck Institute of Neurobiology, now intends to investigate the assembly of these amygdala circuits and how they are able to generate certain behaviors. For this project, Klein will use a unique combination of developmental biology methods and circuit analysis: "My team has great expertise in working with guidance molecules that direct neurons to their destination during brain development. That's where we start."

The amygdala consists of several intermingled but separate circuits that produce opposite behavioral responses. Klein and his team now want to switch the connections between the components of these circuits. As a result, a mouse might perceive innately aversive things, such as the smell of a fox, as a neutral or even attractive cue, or may turn away from the smell of cheese.

Rüdiger Klein aims to redirect neuronal connections during amygdala development with the guidance molecules already studied in his department. The results will reveal the molecules influencing the structure of the amygdala circuits. "In addition, the behavioral changes we expect to observe will allow us to verify the actual functions of these circuits," said Klein.

The structure of the amygdala is very similar between mice and humans. The results of this study in mice can therefore also provide direct information about the human amygdala and its processing of emotions and motivation – and possible malfunctions.

The European Research Council (ERC)

With its Advanced Grants, the European Research Council supports outstanding scientists with at least ten years of excellent research experience. Receiving an ERC Advanced Grant is a great distinction, with only 9.8 percent of the 1881 applicants being awarded this year. Overall, 450 million Euro will go out to 185 successful applications come from 20 nations. In addition to Rüdiger Klein's project, 34 other distinguished proposals came from Germany.

The ERC president, Mauro Ferrari, commented on this year’s Advanced Grants: “I am glad to announce a new round of ERC grants that will back cutting-edge, exploratory research, set to help Europe and the world to be better equipped for what the future may hold. That’s the role of blue sky research. These senior research stars will cut new ground in a broad range of fields, including the area of health. I wish them all the best in this endeavour and, at this time of crisis, let me pay tribute to the heroic and invaluable work of the scientific community as a whole.”

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