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Portretfoto Ingo Willuhn

Ingo Willuhn

Neuroscience Symposium
Willuhn Group

The Neuroscience Symposia are organized weekly by the Netherlands Institute for Neuroscience. The presentations are given by researchers from the institute or by guest speakers. The title and content of the symposium is usually made known in the week prior to the presentation.

The symposium will be held in a hybrid form. A zoom link will be provided by email.

4 pm – Deep-brain stimulation of the mouse internal capsule reveals distinct effects on compulsive behavior and neuronal activity in cortico-striatal circuits with speaker Bastijn van den Boom.

Deep-brain stimulation (DBS) of the internal capsule (IC) is an effective treatment for otherwise therapy-resistant patients suffering from different psychiatric disorders, most notably for patients with severe obsessive-compulsive disorder (OCD). DBS is thought to recruit cortico-striatal circuits but understanding of the specific mechanisms of action of DBS is insufficient.

Here, we systematically examined the effects of different DBS parameters on brain-wide neuron- population activity (wide-field calcium imaging) and single-cell neural-circuit activity (one-photon calcium imaging) in cortico-striatal circuits. We employed SAPAP3 mutant mice (SAPAP3-/-), a versatile model for OCD, that, similar to patients, exhibit compulsive behavior (excessive grooming) and functional deficits in cortico-striatal circuits.

DBS immediately and selectively reduced compulsive grooming in SAPAP3-/- in an intensity- dependent manner and, similar to OCD patients, compulsive behavior reinstated promptly after cessation of DBS. DBS induced instant homogeneous activity patterns in neuron-populations across the dorsal cortex, while single-cell analyses of cortico-striatal circuits revealed complex heterogeneous responses in the spatiotemporal domain. Overall, we identified several functional principles that capture the effects of DBS on cortico-striatal circuits.

Our findings demonstrate that DBS reduces excessive grooming in SAPAP3-/- and indicate recruitment of cortico-striatal circuits as a mechanism for it. We identified general functional principles of DBS, which suggest that anti-compulsive effects of DBS may manifest by means of modulating impaired prefrontal cortex activity, while maintaining general brain functions. Although DBS is an effective therapy, understanding its underlying mechanisms has the potential to significantly improve its efficacy.