Tai A X, Kromer L F
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA.
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA.
Neuroscience. 2014 Aug 22;274:409-18. doi: 10.1016/j.neuroscience.2014.05.039. Epub 2014 Jun 5.
Within the first two postnatal weeks, corticostriatal axons from the primary somatosensory cortex (S1) form topographic projections that organize into characteristic bands of axon terminals in the dorsolateral striatum. Molecules regulating the development of these topographically organized projections are currently unknown. Thus, the present study investigated whether EphA receptor tyrosine kinases, which regulate axonal guidance in the visual system via axon repulsion, could participate in the formation of corticostriatal connections during development. Prior studies indicate that EphA7-expressing striatal neurons are organized into banded compartments resembling the matrisome innervation pattern formed by cortical afferents from the S1 cortex and that ephrin-A5, a known EphA7 ligand, is expressed in a medial (high) to lateral (low) gradient in S1. Thus, we hypothesized that the organization of EphA7-expressing striatal neurons in banded domains provides a repulsive barrier preventing corticostriatal axons containing EphA7-ligands from innervating inappropriate regions of the striatum. To evaluate this, we injected the anterograde tracer, biotinylated dextran amine (BDA), into two locations in medial areas of S1 (the anterior and posterior whisker fields), which are reported to express high levels of ephrin-A5 during development. Injections were made in mouse pups on postnatal day 9 (P9) and the animals were processed for immunohistochemistry on P12. Our data demonstrate that projections from both the forelimb/anterior whisker field and the posterior whisker field avoid EphA7-expressing neurons and terminate in a banded pattern in regions with very low EphA7-expression. We also determined that corticothalamic projections from medial S1 also exhibit a restricted distribution in the thalamus and avoid neurons expressing EphA7. Thus, our results support the hypothesis that the anatomical organization of striatal and thalamic neurons expressing EphA7 receptors restricts the topographic distribution of cortical afferents from medial regions of S1 which express high levels of ephrin-A5.
在出生后的前两周内，来自初级体感皮层（S1）的皮质纹状体轴突形成拓扑投射，这些投射在背外侧纹状体中组织成特征性的轴突终末带。目前尚不清楚调节这些拓扑组织投射发育的分子。因此，本研究调查了通过轴突排斥调节视觉系统中轴突导向的EphA受体酪氨酸激酶是否可能参与发育过程中皮质纹状体连接的形成。先前的研究表明，表达EphA7的纹状体神经元被组织成带状隔室，类似于由S1皮层的皮质传入纤维形成的基质体神经支配模式，并且已知的EphA7配体ephrin-A5在S1中以从内侧（高）到外侧（低）的梯度表达。因此，我们假设带状区域中表达EphA7的纹状体神经元的组织提供了一个排斥屏障，阻止含有EphA7配体的皮质纹状体轴突支配纹状体的不适当区域。为了评估这一点，我们将顺行示踪剂生物素化葡聚糖胺（BDA）注射到S1内侧区域的两个位置（前、后须状区），据报道这些区域在发育过程中表达高水平的ephrin-A5。在出生后第9天（P9）的幼鼠中进行注射，并在P12对动物进行免疫组织化学处理。我们的数据表明，来自前肢/前须状区和后须状区的投射避开表达EphA7的神经元，并在EphA7表达非常低的区域以带状模式终止。我们还确定，来自内侧S1的皮质丘脑投射在丘脑中也表现出受限的分布，并避开表达EphA7的神经元。因此，我们的结果支持这样的假设，即表达EphA7受体的纹状体和丘脑神经元的解剖组织限制了来自表达高水平ephrin-A5的S1内侧区域的皮质传入纤维的拓扑分布。
