Cel 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. Dziedzina nauki medical and health sciencesbasic medicineneurologyparkinson Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-IRG-2008 Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IRG - International Re-integration Grants (IRG) Koordynator FUNDACAO CALOUSTE GULBENKIAN Wkład UE € 100 000,00 Adres AVENIDA BERNA 45A 1067-001 LISBOA Portugalia Zobacz na mapie Region Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Rodzaj działalności Research Organisations Kontakt administracyjny José Mário Leite (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
