NEUROACTION · Neural mechanisms of action learning in mouse models
FP7 — People (Marie Curie Actions)
- Duration
- 2009-08-01 → 2013-07-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-IRG
Lines connect the coordinator with its partners.
Results in brief
Neural mechanisms of action learning in mouse models
Executive Summary: The process of perfecting an action through repetition leads to more accurate, precise and faster performance. The neural circuits involved in the consolidation of these different aspects of skill learning remain somewhat unknown. Using mice expressing fluorescent proteins in direct and indirect striatal circuits, we found that extended training is accompanied by subregion-specific circuit plasticity in the dorsal striatum, with glutamatergic input to the indirect pathway being more potentiated late in learning. However, during the process of doing the experiments of the grant we realized that while the rotarod allows for the reliable study of skill consolidation, it does not permit easily the dissection of the different aspects of motor learning described above. We therefore developed a self-paced operant task in which mice have to press a lever at increasingly faster speeds to obtain food reward. We used several versions of this task in combination with circuit-specific optogenetic manipulations to investigate which pathways are involved in initiating a well-learned skill or performing it. We found that inhibiting or stimulating either the direct and indirect pathway before affects the initiation of the action sequence. However, after sequence initiation we found that inhibiting or stimulating the direct and indirect pathways of striatum had dichotomous effects. Finally, we have also developed a method to record from identifiable of cell types in vivo, and find that different neurons from the direct and indirect pathway are differentially involved at different phases of skill execution (initiation or performance). These findings have important implications for understanding the learning and execution of skilled movements, and the impairments observed in basal ganglia disorders like Parkinson’s and Huntington’s disease.
Data: CORDIS, © European Union
Project objective
The learning of novel skills is characterized by an initial stage of rapid improvement in performance, followed by a phase of more gradual improvements as the skills are automatized and performance asymptotes. Although the striatum has been implicated in skill learning, the detailed mechanisms and circuits underlying its role in the acquisition and consolidation of skills are not understood. Using in vivo striatal recordings in mice we observed region-specific changes in neural activity during the different phases of skill learning. We verified using ex vivo recordings from medium spiny striatal neurons in brain slices of trained mice that the changes observed in vivo corresponded to long-lasting and training-specific changes in excitatory synaptic transmission in the striatum. Our preliminary data indicates that these changes may be differentially expressed in different output pathways of the striatum, i.e. in D2 receptor-expressing striatopalidal neurons (indirect pathway) versus D1-expressing striatonigral neurons (direct pathway). We propose to: 1) use BAC transgenic mice that express GFP in the direct or indirect pathway to discriminate if the long-lasting plasticity observed during acquisition and consolidation of a skill occurs preferentially in one of the pathways, 2) generate and use cell-type specific channelrodhopsin and halorodhopsin transgenic mice to investigate the involvement of the direct and indirect pathway in the acquisition and automatization of skills, and 3) record in vivo from identified striatopallidal and striatonigral neurons, by means of either optogenetic stimulation, and determine if the direct and indirect pathway are differentially active during the acquisition and automatization of a skill. These experiments will help us understand the role of the direct and indirect pathway in voluntary and automatic movement, with important implications for understanding the origin of movement dysfunction in Parkinson’s and Huntington’s disease.
Original text from CORDIS.
Participants
- FUNDACAO CALOUSTE GULBENKIAN · LisboaCoordinatorPortugal
Links
Data: CORDIS, © European Union