Role of corticostriatal system components in response flexibility, control of learned behavior and neurocognitive deficits.

The corticostriatal system has been suggested to play a role in cognitive functions, but its importance for spatial cognition has been scarcely studied. Different neurological and psychiatric diseases, such as Parkinson’s disease and schizophrenia, are related to (cortico)striatal dysfunctions. These disorders are characterized by motor impairments and psychotic episodes, but cognitive problems occur as well, specifically during early phases of these disorders. These cognitive deficits are largely intractable with available treatment, remain chronically present throughout the course of the disease, and are linked to poor functional prognosis of patients.

The most important goal of this dissertation was to investigate the corticostriatal system in relation to spatial-cognitive functions and behavioural flexibility. We reported differential and time-dependent involvement of the dorsomedial (DMS) and dorsolateral (DLS) parts of the striatum in spatial cognition. DMS, but not DLS, was crucial to acquire spatial information and subsequent deployment of spatial search strategies during early learning phases. Furthermore, we revealed decreased DMS involvement as learning progressed or when adjustments in navigation were required. These results suggest a role for DMS during spatial navigation, when contextual information is used to develop and use a spatial search strategy, and when behaviour is still flexible. DMS receives direct input from the anterior cingulate cortex (aCC) and both Arc expression levels and aCC/DMS disruption lesions demonstrated that aCC/DMS connectivity is crucial for spatial cognition.

By and large, our experiments identified DMS and aCC/DMS connectivity as central anatomical substrates in response flexibility and spatial learning. These findings relate to cognitive deficits of disorders with corticostriatal (dys)functioning and may show the way for possible treatment of these devastating disorders.