| Reference code: | PT/FB/BL-2012-192.05 |
| Location: | Arquivo PCA - Pasta 15/2012
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Title:
| Conditional Foxp2 deletions differentially affect motor-skill learning
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| Publication year: | 2015
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URL:
| http://www.google.pt/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0CCgQFjABahUKEwjpjL6ztuLGAhXBFtsKHTfPC3Q&url=http%3A%2F%2Fwww.ibmc.up.pt%2Fspn2015%2Fabstract_book_04.06.2015.pdf&ei=vBepVem-HMGt7Aa3nq-gBw&usg=AFQjCNGZI4FQ_pCcLqX1KG1_YiZCz1Ez0Q&sig2=XB4pwMCQn3GDwOaDl8VYzw&bvm=bv.98197061,d.ZGU
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| Abstract/Results: | ABSTRACT:
Disruptions of the FOXP2 gene cause a rare speech and language disorder. In the KE family a heterozygous FOXP2 mutation is dominantly inherited and affected individuals have difficulty producing the sequences of orofacial motor movements necessary for fluent speech. This is considered a core deficit of the disorder, although other expressive and receptive language problems also exist. The FOXP2 transcription factor is expressed in cortico-striatal/ -cerebellar circuits required for sensorimotor integration and motor-skill learning, and imaging studies have identified structural abnormalities in several of these regions in affected KEfamily members. FOXP2 is also highly conserved in a number of other vertebrate species, where expression is seen both during development and in adulthood. Mice carrying the KE-family mutation have motor-skill learning deficits and lack striatal long-term depression. They also have abnormally high striatal activity in vivo which is aberrantly modulated during the learning of a motor task. Juvenile zebra finches show increased FoxP2 expression during the song learning period in striatal nucleus Area X, and FoxP2 knockdown in this region results in inaccurate and incomplete song imitation. FoxP2 knockdown in Area X of mature birds renders song more variable and abolishes the mediation of song by social context. We used a conditional Foxp2 mouse line to selectively delete Foxp2 from the cortex, striatum or cerebellar Purkinje cells. This genetic approach was combined with an operant task where a sequence of 8 lever presses must be completed to obtain a food reinforcer. After 12 days a time constraint was added and the sequence had to be performed at increasingly high speeds. Both cerebellar and striatal Foxp2 mutants showed a reduced rate of lever pressing during training compared to controls. However, analyses of behavioural microstructure revealed that in cerebellar mutants pressing of all speeds is altered, whereas in striatal and cortical mutants rapid pressing is primarily affected. Furthermore, in striatal mutants rapid pressing also becomes more variable. In a separate experiment we used a tamoxifen-inducible Cre to disrupt Foxp2 globally in adult mice. Around one third of Cre positive animals died, with the first deaths occurring 6 weeks after tamoxifen administration. Surviving animals appeared healthy but showed a reduced press rate on the motor-sequence learning task.
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| Accessibility: | Document exists in file
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Language:
| eng
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Author:
| French, C.
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Secondary author(s):
| Correia, M., Gomez-Marin, A., Feliciano, C., Paixão, V., Jin, X., Fisher, S. E., Costa, R. M.
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Document type:
| Abstract book
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Number of reproductions:
| 1
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Reference:
| French, C., Correia, M., Gomez-Marin, A., Feliciano, C., Paixão, V., Jin, X., Fisher, S. E., & Costa, R. M. (2015). Abstract book of the XIV Meeting of the Portuguese Neuroscience Society,4-5th June 2015, Póvoa de Varzim, Portugal (p. 127).
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| Indexed document: | No
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| Keywords: | Motor-skill learning / Foxp2
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Conditional Foxp2 deletions differentially affect motor-skill learning |