Freie Universität Berlin, Laboratory of Animal Behavior, Berlin, Germany.
Genes Brain Behav. 2010 Oct;9(7):732-40. doi: 10.1111/j.1601-183X.2010.00607.x. Epub 2010 Jul 6.
Mutations in the gene encoding the transcription factor FoxP2 impair human speech and language. We have previously shown that deficits in vocal learning occur in zebra finches after reduction of FoxP2 in Area X, a striatal nucleus involved in song acquisition. We recently showed that FoxP2 is expressed in newly generated spiny neurons (SN) in adult Area X as well as in the ventricular zone (VZ) from which the SN originates. Moreover, their recruitment to Area X increases transiently during the song learning phase. The present report therefore investigated whether FoxP2 is involved in the structural plasticity of Area X. We assessed the proliferation, differentiation and morphology of SN after lentivirally mediated knockdown of FoxP2 in Area X or in the VZ during the song learning phase. Proliferation rate was not significantly affected by knockdown of FoxP2 in the VZ. In addition, FoxP2 reduction both in the VZ and in Area X did not affect the number of new neurons in Area X. However, at the fine-structural level, SN in Area X bore fewer spines after FoxP2 knockdown. This effect was even more pronounced when neurons received the knockdown before differentiation, i.e. as neuroblasts in the VZ. These results suggest that FoxP2 might directly or indirectly regulate spine dynamics in Area X and thereby influence song plasticity. Together, these data present the first evidence for a role of FoxP2 in the structural plasticity of dendritic spines and complement the emerging evidence of physiological synaptic plasticity in FoxP2 mouse models.
基因突变导致转录因子 FoxP2 功能缺失，从而损害人类的言语和语言能力。我们之前的研究表明，在参与鸣禽歌曲学习的纹状体核团 X 区 FoxP2 表达量减少后，斑马雀的发声学习能力受损。我们最近发现 FoxP2 不仅在成年纹状体核团 X 区新生的棘状神经元（spiny neurons，SN）中表达，也在 SN 的起源处脑室区（ventricular zone，VZ）中表达。此外，它们在歌曲学习阶段向 X 区的募集会短暂增加。因此，本研究旨在探讨 FoxP2 是否参与 X 区的结构可塑性。我们通过在歌曲学习阶段，利用慢病毒介导的 FoxP2 敲低，在 X 区或 VZ 中评估 SN 的增殖、分化和形态。VZ 中 FoxP2 的敲低对增殖率没有显著影响。此外，VZ 和 X 区的 FoxP2 减少都不会影响 X 区的新生神经元数量。然而，在精细结构水平上，X 区的 SN 棘突数量在 FoxP2 敲低后减少。当神经元在分化前，即在 VZ 中作为神经母细胞时，接受敲低，这种效应更加明显。这些结果表明，FoxP2 可能直接或间接调节 X 区的棘突动态，从而影响鸣曲可塑性。总的来说，这些数据首次证明了 FoxP2 在树突棘状结构可塑性中的作用，并补充了 FoxP2 小鼠模型中生理突触可塑性的新兴证据。
