Molecular Mechanisms of Basal Ganglia Regeneration in Songbirds

描述(申请人提供)：在研究基底节通路在习得性发声交流中的作用时，我们发现了一个意想不到的现象：在神经毒性损伤之后，鸟类纹状体自我恢复。据我们所知，这种现象在哺乳动物的大脑中是前所未有的。在这里，我们建议研究这种恢复的机制：这实际上是新的神经元再生还是来自周围区域的神经元入侵。此外，我们将确定伴随着行为(歌唱)恢复的这种恢复的时间进程。我们将确定恢复的纹状体中的细胞组织是否与完整的纹状体中的相同。最后，我们将测试这种恢复是针对神经毒性损害的，还是更普遍的鸟类纹状体方面的。由于鸟类纹状体包含的神经元在电生理和分子特性上与哺乳动物纹状体相似，该项目有望影响我们对大脑再生的理解。这项研究与公共卫生的相关性在于，我们将找到修复受损的基底节脑区的潜在方法，特别是纠正语言缺陷。这项研究将主要在斯洛伐克与Lubica Kubikova合作在斯洛伐克科学院动物生物化学和遗传学研究所进行，作为NIH#R01 DC007218-01补助金的延伸。

DESCRIPTION (provided by applicant): While studying the role the basal ganglia pathway in learned vocal communication, we discovered an unexpected phenomenon: following neurotoxic lesions, the avian striatum recovered itself. This phenomenon, as far as we know, is unprecedented in the mammalian brain. Here we propose to investigate the mechanisms of this recovery: whether this is in fact new neuron regeneration or neuron invasion from the surrounding areas. Further we will determine the time course of this recovery accompanied with the behavioral (song) recovery. We will identify whether the cellular organization in the recovered striatum is the same as in intact striatum. Finally, we will test whether the recovery is specific to the neurotoxic lesion or if it is a more general aspect of the avian striatum. As the avian striatum contains neurons similar in their electrophysiological and molecular properties to their mammalian counterparts, the project is expected to impact our understanding of brain regeneration. The relevance of this research to public health is that we would find potential ways to repair damaged basal ganglia brain areas, and in particular for correcting speech deficits. This research will be done primarily in Slovakia at the Institute of Animal Biochemistry and Genetics at the Slovak Academy of Sciences in collaboration with Lubica Kubikova, as an extension of NIH grant #R01 DC007218-01.