Willuhn Group

The Neuromodulation & Behavior group is driven by the question: “What drives our behavior?”. Specifically, the group is interested in how our brain controls motivated behavior and under what circumstances our behavior occurs seemingly uncontrolled or maladapted. In this context, the scientific focus lies on how the release of the neurotransmitter dopamine (and other neuromodulators such as serotonin) regulates cortico-basal ganglia networks under normal (e.g., reward learning, decision making), as well as pathological conditions (e.g., obsessive-compulsive disorder (OCD) and other disorders that exhibit compulsive behavior). The group pursues these goals by collecting a range of neurobiological measurements in awake behaving rodents (using voltammetry, electrophysiology, and fluorescence imaging) and by probing neural mechanisms with optogenetic, chemogenetic, and pharmacological interventions, as well as high-frequency electrical deep-brain stimulation that can also be applied in humans.

The Willuhn group conducts its scientific research at the Netherlands Institute for Neuroscience (NIN) but is also embedded in the Psychiatry Department of the Amsterdam UMC and, therefore, has close ties with clinicians and clinical researchers, providing optimal conditions for a translational and multidisciplinary approach. Specifically, we aim to translate clinical findings from studies in humans into relevant animal models, and vice versa. To study behaviors relevant for psychiatric disorders, with a focus on compulsive and impulsive behavior, the group employs a variety of cutting-edge methods for in-vivo brain recordings and manipulations in rodent models (both rats and mice). Such recordings and manipulations are carried out while rodents perform in sophisticated, custom-designed behavioral paradigms that enable translation to human subjects.

Furthermore, the team investigates the therapeutic brain mechanisms of deep-brain stimulation, an innovative therapeutic approach in psychiatry, and is interested in studying the brain mechanisms of other neuromodulatory treatments used in psychiatry (e.g., transcranial magnetic stimulation, ultrasonic stimulation). The long-term goal is that these approaches will identify the neural circuits underlying specific psychiatric symptoms and offer new, highly targeted pathways for therapy in psychiatric patients.
Compulsivity and impulsivity are endophenotypes that are implicated in dysfunctional behavior central to multiple psychiatric disorders, such as OCD, substance and behavioral addictions, hoarding, eating disorders, or skin picking. Furthermore, the Willuhn lab is interested in mechanisms through which actions become automatic (i.e., habit formation) and how the brain shapes motivation and action in response to rewarding and aversive stimuli, thereby guiding both appetitive and avoidance behavior. The Willuhn group approaches its psychiatric research in rodents from different angles. On one hand, genetic manipulations of genes known to be strongly involved in psychiatric disorders are utilized to create mouse models. On the other hand, behavioral conditioning is utilized to induce behaviors of interest gradually (and non-genetically) and monitor their development.

Keywords: Dopamine, Serotonin, Basal ganglia, Striatum, Prefrontal cortex, Obsessive-compulsive disorder, Compulsivity, Impulsivity, Habit formation, Motivation, Reinforcement learning, Decision making, Deep-brain stimulation (DBS), Transcranial magnetic stimulation (TMS).

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