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Willuhn Group

800,000 euros for the Willuhn group

The Willuhn group receives 800,000 euros for their research into a better understanding of neuronal connectivity and function in complex neuronal networks relevant in psychiatric disorders. The research is part of a larger project named BRAINSCAPES, which is a collaboration between VU University, Utrechtv University, Leiden University, Amsterdam UMC, TU Delft, the Hubrecht Institute, and the Netherlands Institute for Neuroscience.

“In the BRAINSCAPES project, our group will conduct behavioral experiments using transgenic rat lines designed to manipulate the dopamine system with chemo- and opto-genetic tools combined with in vivo measuring tools such as fast-scan cyclic voltammetry, electrophysiology, and calcium imaging” explains Ingo Willuhn. “The goal of these studies is to ask how specific types of neural cells are engaged and in that way they are responsible for pathological behavior, observed in animal models for eating-related disorders, substance abuse, and depression.”

BRAINSCAPES

Recent genetic discovery studies have provided unprecedented insight into the genes involved in brain disorders. The next step is to use this knowledge for gaining mechanistic disease insight. In BRAINSCAPES, we will develop novel analytic and experimental tools to study the functional consequences of risk genes for the function of specific cells, their circuits, and functional output. We aim to provide insight into the molecular and cellular basis of complex brain disorders that can be used to design novel treatments.

INNOVATIVE SCIENTIFIC RESEARCH

The contribution is part of the Gravitation program which is funded by the Ministry of Education, Culture and Science. The Dutch Research Council (NWO) selects the research groups on behalf of the Ministry. One of the pillars of the program is the collaboration across disciplines and universities. With the funding, researchers will be able to collaborate in top-level, multidisciplinary university research for a period of ten years.

 

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Willuhn Group

Neuromodulation & Behavior

This pre-clinical research group headed by Ingo Willuhn is embedded in a larger clinical research team at the AMC department of Psychiatry. The group is driven by the question: “How do we control our behavior?”. Specifically, the Neuromodulation and Behavior group is interested in the neurobiology of compulsive behavior and in mechanisms through which actions become automatic with a focus on basal ganglia function and dopamine signaling. Furthermore, the group studies the effects of deep-brain stimulation (DBS) on brain and behavior.

What is compulsivity? Compulsivity is behavior that is out of control, behavior we perform despite not wanting to perform it or despite its negative outcome. Compulsive behavior is performed persistently, repetitively, and inflexibly. But how does compulsivity develop? What is its neurobiological basis? To answer these questions, we investigate different aspects of compulsivity (e.g., automation of behavior, cognitive (in-)flexibility) and measure/modulate neuronal activity in the brain simultaneously.

Compulsivity is a core feature in several neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) and drug addiction. In otherwise therapy-resistant patients of such disorders, DBS has been effective. However, our understanding of the mechanisms of action of DBS is still limited. Therefore, we aim to investigate how DBS affects compulsivity and what the neurobiological basis of these effects is.

Our group has a strong collaborative relationship to the Department of Psychiatry at the Amsterdam Medical Center (AMC) lead by Damiaan Denys and therefore has close ties with clinicians and clinical researchers, providing optimal conditions for a translational and multidisciplinary approach. Specifically, we translate clinical findings from studies in humans into relevant animal models, and vice versa we aim to apply our conclusions in the clinical setting. At the very core of our research is the study of rodent behavior. On one hand, we test compulsive behavior itself by using behavioral, (e.g., signal attenuation, schedule-induced polydipsia), pharmacological (drug self-administration), and genetic (SAPAP3-KO mice) animal models. On the other hand, we study “normal’ behavioral faculties such as habit formation, response flexibility, emotion, and cognition (e.g., elevated plus maze, operant chambers) that may contribute to compulsivity when dysregulated. We combine behavioral testing with state-of-the-art research tools including diverse methods for brain stimulation (e.g., DBS, chemogenetics, optogenetics), neurochemical measurements (e.g., microdialysis, fast-scan cyclic voltammetry), calcium imaging (implantable miniaturized microscopes), and electrophysiological recordings (e.g., single-unit activity, local field potentials (LFPs)). Furthermore, we use functional magnetic resonance imaging (fMRI) in rodents to detect the effects of drugs and DBS throughout the brain.

 

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