Objetivo
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.
Ámbito científico
Convocatoria de propuestas
FP7-PEOPLE-IRG-2008
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Régimen de financiación
MC-IRG - International Re-integration Grants (IRG)Coordinador
1067-001 LISBOA
Portugal