Servicenavigation

Project Details

Back

Projekt Print View

Modulating the shift from goal-directed to habitual behaviors by manipulation of dopaminergic striatonigral loops

Subject Area Molecular Biology and Physiology of Neurons and Glial Cells
Cognitive, Systems and Behavioural Neurobiology
Term from 2018 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 406901759
 
Final Report Year 2024

Final Report Abstract

Behaviours such as tying shoelaces or speaking require multiple steps of learning until they are efficient. This includes an initial motivation phase, a “goal-directed” phase, in which environment and actions are associated with outcomes, and a “habitual” phase in which behaviours are automatized. This type of learning has been intensely studied for decades, revealing cortico-basal ganglia circuits (CBGs) as the essential neuronal substrate and dopamine as the key neurotransmitter. Thereby, information on motivation, environment and actions from the cortex is integrated with information on reward from dopaminergic neurons by medium spiny neurons of the striatum and relayed back to the cortex via output nuclei of the basal ganglia and the thalamus. CBGs are topographically organised, so that for example limbic, associative and sensorimotor areas of the cortex project to the ventromedial (VMS), dorsomedial (DMS) and dorsolateral striatum (DLS), respectively. These are thought to be especially required during the initial, goal directed and habitual learning phase, respectively. A canonical hypothesis how these loops and their learning phases are connected is their bridging by dopaminergic neurons that project and hence provide reward information to the “next” loop. However, this plausible hypothesis has so far not been addressed at a functional or molecular level. Furthermore, it was shown that CBG-dependent learning is affected by the transcription factor Foxp2 that is expressed in medium spiny neurons and associated with speech development and evolution. Remarkably, mice “humanized” for two amino acid changes in Foxp2 show an accelerated transition from goal-directed to habitual learning. However, it is not known how this affects CBGs at the functional or molecular level. To address these challenging questions, we combined our expertise in behavioural assays (Burguière lab) and gene expression profiling (Enard lab). We could decisively improve, validate and apply these methods resulting in twelve publications during the project. It also enabled us to profile a total of 870 striatal samples collected from the VMS, DMS and DLS at a goal-directed, intermediate and habitual learning stage in mice carrying humanized, non-functional or wildtype Foxp2 alleles. Importantly, we also profiled non-learning control mice. This is by far the most comprehensive expression profile of the learning striatum. While we find over thousand expression changes especially during the goal-directed phase, these have little - if any - region-specificity. Hence, a sequential recruitment and spiralling CBG loops are not reflected at the level of gene expression. We also identify over hundred genes specific to humanized Foxp2, opening new windows into the evolution of speech. In summary, the project developed methodology and data that resulted in fundamental insights into the function and evolution of CBG-dependent learning.

Publications

 
 

Additional Information

© 2026 DFG Disclaimer / Copyright / Privacy Policy

Textvergrößerung und Kontrastanpassung