Department of Animal Behavior, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Sci Rep. 2020 Mar 16;10(1):4787. doi: 10.1038/s41598-020-61740-6.
The transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits. FOXP2 mutations are associated with specific speech and language impairments. In songbirds, experimentally altered FoxP2 expression levels in the striatal song nucleus Area X impair vocal learning and song production. Overall FoxP2 protein levels in Area X are low in adult zebra finches and decrease further with singing. However, some Area X medium spiny neurons (MSNs) express FoxP2 at high levels (FoxP2 MSNs) and singing does not change this. Because Area X receives many new neurons throughout adulthood, we hypothesized that the FoxP2 MSNs are newly recruited neurons, not yet integrated into the local Area X circuitry and thus not active during singing. Contrary to our expectation, FoxP2 protein levels did not predict whether new MSNs were active during singing, assayed via immediate early gene expression. However, new FoxP2 MSNs had more complex dendrites, higher spine density and more mushroom spines than new FoxP2 MSNs. In addition, FoxP2 expression levels correlated positively with nucleus size of new MSNs. Together, our data suggest that dynamic FoxP2 levels in new MSNs shape their morphology during maturation and their incorporation into a neural circuit that enables the maintenance and social modulation of adult birdsong.
转录因子 FOXP2 对于皮质-纹状体回路的形成和功能至关重要。FOXP2 突变与特定的言语和语言障碍有关。在鸣禽中，实验性地改变纹状体歌唱核区 X 中的 FoxP2 表达水平会损害发声学习和歌唱产生。成年斑马雀的区 X 中的整体 FoxP2 蛋白水平较低，并且随着歌唱进一步降低。然而，一些区 X 中的中型多棘神经元 (MSNs) 高水平表达 FoxP2（FoxP2 MSNs），而歌唱不会改变这一点。由于区 X 在整个成年期接收许多新神经元，我们假设 FoxP2 MSNs 是新招募的神经元，尚未整合到局部区 X 电路中，因此在歌唱期间不活跃。与我们的预期相反，FoxP2 蛋白水平并不能预测新 MSNs 在歌唱时是否活跃，通过即时早期基因表达进行测定。然而，新的 FoxP2 MSNs 具有更复杂的树突、更高的棘突密度和更多的蘑菇棘突，而新的 FoxP2 MSNs 则没有。此外，FoxP2 表达水平与新 MSNs 的核大小呈正相关。总之，我们的数据表明，新 MSNs 中动态的 FoxP2 水平塑造了它们在成熟过程中的形态，以及它们在一个能够维持和调节成年鸟鸣的神经网络中的整合。
