Neuropilin 2 Signaling Mediates Corticostriatal Transmission, Spine Maintenance, and Goal-Directed Learning in Mice
Neuropilin 2 Signaling Mediates Corticostriatal Transmission, Spine Maintenance, and Goal-Directed Learning in Mice
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DOI：
10.1523/jneurosci.1006-19.2019
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发表时间：
2019-11-06
影响因子：
5.3
通讯作者：
Shah, Fulva
中科院分区：
文献类型：
--
作者：
Assous, Maxime;Martinez, Edward;Shah, Fulva
纹状体是基底神经节的主要输入结构，接受来自皮质和丘脑的大量兴奋性输入。纹状体皮质输入的发育和维持对纹状体的所有功能至关重要，包括多种形式的感觉运动整合、学习和动作控制。调节皮质纹状体突触传递的分子机制尚不清楚。在这里，我们展示了引导线索，Semaphorin 3F及其受体Neuropilin 2(Nrp2)，影响成年雄性和雌性小鼠树突棘的维持、皮质纹状体的短期可塑性和学习。我们发现Nrp2在成体V层锥体神经元、皮质纹状体终末以及发育和成体纹状体棘投射神经元(SPN)中含量丰富。Nrp2的缺失增加了SPN的兴奋性和脊椎数量，减少了皮质纹状体突触的短期易化，并损害了工具性任务中的目标定向学习。在成年V层皮质神经元中选择性地急性缺失Nrp2会导致Nrp2(-/-)小鼠皮质纹状体突触中树突棘数量和突触前修饰的类似增加，但不影响SPN的内在兴奋性。此外，Nrp2的条件性丢失损害了加速轮杆上的感觉运动学习，而不影响目标导向的工具性学习。总之，我们的结果确认Nrp2信号对于皮质纹状体通路的发展和维持是必不可少的，并可能对与皮质纹状体通路和Semaphorin信号相关的神经发育障碍提供新的见解。
The striatum represents the main input structure of the basal ganglia, receiving massive excitatory input from the cortex and the thalamus. The development and maintenance of cortical input to the striatum is crucial for all striatal function including many forms of sensorimotor integration, learning, and action control. The molecular mechanisms regulating the development and maintenance of corticostriatal synaptic transmission are unclear. Here we show that the guidance cue, Semaphorin 3F and its receptor Neuropilin 2 (Nrp2), influence dendritic spine maintenance, corticostriatal short-term plasticity, and learning in adult male and female mice. We found that Nrp2 is enriched in adult layer V pyramidal neurons, corticostriatal terminals, and in developing and adult striatal spiny projection neurons (SPNs). Loss of Nrp2 increases SPN excitability and spine number, reduces short-term facilitation at corticostriatal synapses, and impairs goal-directed learning in an instrumental task. Acute deletion of Nrp2 selectively in adult layer V cortical neurons produces a similar increase in the number of dendritic spines and presynaptic modifications at the corticostriatal synapse in the Nrp2(-/-) mouse, but does not affect the intrinsic excitability of SPNs. Furthermore, conditional loss of Nrp2 impairs sensorimotor learning on the accelerating rotarod without affecting goal-directed instrumental learning. Collectively, our results identify Nrp2 signaling as essential for the development and maintenance of the corticostriatal pathway and may shed novel insights on neurodevelopmental disorders linked to the corticostriatal pathway and Semaphorin signaling.