| Reference code: | PT/FB/BL-2012-192.04 |
| Location: | Arquivo PCA - Pasta 15/2012
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Title:
| Effects of Foxp2 disruption in selected brain regions and in adulthood
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| Publication year: | 2014
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URL:
| http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=4c006652-77a4-47b0-88ee-abcc10f86f2d&cKey=97f4a710-c929-47d4-acfd-c5e0a54fc9db&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
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| Abstract/Results: | ABSTRACT:
Disruptions of the FOXP2 gene cause a rare speech and language disorder. A core feature of this disorder is difficulty in producing the sequences of orofacial motor movements necessary for fluent speech, although other expressive and receptive language problems are also present. Imaging studies have shown structural abnormalities in the caudate nucleus and ventral cerebellum, as well as altered patterns of activation during language-based tasks. FOXP2 encodes a transcription factor which is expressed in the cortico-striatal and cortico-cerebellar circuits required for sensorimotor integration and motor-skill learning. This neural expression pattern, and the FOXP2 protein sequence, are highly conserved in other vertebrate species such as mice and songbirds. Mice carrying a heterozygous point mutation in Foxp2 (the KE-family mutation) have motor-skill learning deficits and lack striatal long-term depression. We also found aberrant striatal activity in vivo during the learning of a motor task. Juvenile zebra finches show increased FoxP2 expression in AreaX of the striatum during the song learning-period, and FoxP2 knockdown in AreaX results in inaccurate and incomplete imitation of the tutor bird's song. FoxP2 knockdown in AreaX of mature birds abolishes the mediation of song by social context and suggests that FoxP2 function is important in adulthood as well as during development. We previously generated a conditional Foxp2 line and have used it to disrupt Foxp2 in selected brain regions (cortex, striatum or cerebellar Purkinje cells), and at a defined time point (adulthood). This genetic approach is being combined with an operant motor-sequence learning task where mice must complete a sequence of 8 lever presses to obtain a food reward. After 12 days a time constraint is added and the sequence must be performed at increasingly high speeds. Both cerebellar and striatal Foxp2 mutants show a reduced rate of lever pressing during training compared to controls. However, analyses of behavioural microstructure revealed that whilst pressing of all speeds is altered in cerebellar mutants, in striatal mutants it is primarily rapid pressing that is affected. These data indicate that Foxp2 function in distinct subcircuits differentially affects motor-skill learning. We disrupted Foxp2 globally in adult mice using a tamoxifen-inducible Cre. Preliminary data indicate that homozygous adult knockouts are viable, unlike other Foxp2 homozygous mutants which die at 3-4 weeks of age. Work is ongoing to investigate motor-sequence learning and other aspects of behaviour in these animals.
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| Accessibility: | Document does not exist in file
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Language:
| eng
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Author:
| French, C.
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Secondary author(s):
| Gomez-Marin, A., Correia, M., Feliciano, C., Paixão, V., Jin, X., Fisher, S. E., Costa, R. M.
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Document type:
| Online abstract
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Number of reproductions:
| 1
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Reference:
| French, C., Gomez-Marin, A., Correia, M., Feliciano, C., Paixão, V., Jin, X., Fisher, S. E., & Costa, R. M. (2014, November). Effects of Foxp2 disruption in selected brain regions and in adulthood. Poster presented at the Society for Neuroscience Annual Meeting, Washington, DC, USA. Abstract retrieved from http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=4c006652-77a4-47b0-88ee-abcc10f86f2d&cKey=97f4a710-c929-47d4-acfd-c5e0a54fc9db&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
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| Indexed document: | No
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| Keywords: | Foxp2 / Speech and language / Motor-sequence learning
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