Bidirectional manipulation of mTOR signaling disrupts socially mediated vocal learning in juvenile songbirds

被引:26
作者
Ahmadiantehrani, Somayeh [1 ,2 ]
London, Sarah E. [1 ,2 ,3 ]
机构
[1] Univ Chicago, Dept Psychol, Chicago, IL 60637 USA
[2] Univ Chicago, Inst Mind & Biol, Chicago, IL 60637 USA
[3] Univ Chicago, Grossman Inst Neurosci Quantitat Biol & Human Beh, Chicago, IL 60637 USA
关键词
zebra finch; development; critical period; rapamycin; learning; AUTISM SPECTRUM DISORDERS; FEMALE ZEBRA FINCHES; MAMMALIAN TARGET; BEHAVIORAL PHENOTYPES; TRANSLATIONAL CONTROL; TAENIOPYGIA-GUTTATA; SYNAPTIC PLASTICITY; SONG PRESENTATION; MOUSE MODELS; MEMORY;
D O I
10.1073/pnas.1701829114
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Early life experiences can have long-lasting behavioral consequences because they are encoded when the brain is most malleable. The mechanistic target of rapamycin (mTOR) signaling cascade modulates experience-dependent synaptic plasticity, among other processes. mTOR has been almost exclusively examined in adult rodent learning models, but may be especially important in organizing neural circuits required for developmental acquisition of meaningful complex behaviors. It is among the most commonly implicated factors in neurodevelopmental autism spectrum disorders (ASD), characterized, in part, by distinct social and communication phenotypes. Here, we investigated mTOR in juvenile zebra finch songbirds. Much as children learn language, young male zebra finches need to interact socially with an adult tutor to learn a meaningful song. The memory of the tutor's song structure guides the juvenile's own song, which it uses to communicate for the rest of its life. We hypothesized that mTOR is required for juveniles to learn song. To this end, we first discovered that hearing song activates mTOR signaling in a brain area required for tutor song memorization in males old enough to copy song but not in younger males or females, who cannot sing. We then showed that both inhibition and constitutive activation of mTOR during tutor experiences significantly diminished tutor song copying. Finally, we found that constitutive mTOR activation lowered a behavioral measure of the juvenile's social engagement during tutor experiences, mirroring the relationship in humans. These studies therefore advance understanding about the effects of experience in the context of neurodevelopmental disorders and typical neural development.
引用
收藏
页码:9463 / 9468
页数:6
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