Molecular and behavioral profiling of subthalamic neurocircuitry

The subthalamic nucleus (STN) is an excitatory brain structure serving as a key regulator of movement. Using an optogenetic approach in mice, we could recently confirm this.

However, we also found that, when given a choice, mice do their utmost to avoid excitation of the STN, as if this is perceived as aversive. Our discovery suggests that the STN is part of the brain aversion and emotion systems.

This exciting finding is a potential game-changer because it can help us understand neurobiological mechanisms underlying emotion, and how emotions guide decision-making in motivated behavior.

We now propose that the STN forms a strongly heterogeneous brain hub at the intersection of motor, cognitive and emotional functions.

My project will explore the possibility that different STN neurons, identified by molecular heterogeneity, are committed to different aspects of behavioral regulation.

Using state-of-the-art viral-genetics approaches in mice, reinforced to molecular precision, we will test three hypotheses: 1) the STN is composed of molecularly defined types of neurons that engage in distinct circuitry through which they impact on motivated behavior; 2) the STN is part of a limbic-autonomic network of emotional manifestation; 3) aberrant STN activity is the direct cause of certain affective and motor symptoms and could be used as predictive marker of brain disorder.

The results are expected to advance knowledge of neurobiological underpinnings of behavior on several levels.