De Zeeuw group

General description research

The CCC group is interested in the role of the cerebellum in cognitive functions and related disorders. In contrast to the prevailing view that the cerebellum is purely a computational machine for controlling sensorimotor processes, evidence is emerging that the cerebellum also plays a role in facilitating cognitive functions. For example, the CCC group has shown that the lateral cerebellar nucleus contributes to covert attention and action perception, while the medial cerebellar nucleus is critical for discrimination learning, decision-making and motor planning. The CCC group is currently trying to unravel which processes in the cerebellar cortex are essential for these forms of cognitive behaviours.

Psychiatric symptoms (or disorders) the group is interested in

One of the types of mental disorders that is strongly affected by cerebellar disfunction is autistic spectrum disorder (ASD). The CCC group has shown that Purkinje cell – specific abortion of the expression of Shank2 in mice leads to symptoms associated with ASD, including repetitive behaviour, social communication deficits and reduced cognitive flexibility. These deficits come with abnormal firing of Purkinje cells and impairments in associative conditioning, such as Pavlovian eyeblink conditioning. The same behavioural deficits can be observed in patients suffering from ASD.

Technical approaches

ASD, which can result from one or more mutations of well over 300 different genes, can be readily detected in patients with an App recently developed by BlinkLab (blinklab.org). Using this App, we have shown that these patients show the same types of deficits as observed in the ASD mouse models that we study. These include changes in both spontaneous eye movements and the conditioning of cerebellar reflexes. The related mouse models are usually studied with the conditioning eyeblink paradigms that we developed for testing their capacity for generating associative behaviour. However, more recently we have also been verifying them with other tasks directly related to social behaviours; these include the three-chamber task and the modified elevated gap interaction test.

Keywords: Autism Spectrum Disorder (ASD), cerebellum, BlinkLab, eyeblink conditioning, Purkinje cells

List of the matching research domains and/or disorders: Working memory (flexible updating), Social communication (reception of facial communication), Perception and understanding of others (action perception), Sleep-wakefulness (procedural learning), and Motor actions (action planning and selection).