Asymmetric cortical projections to striatal direct and indirect pathways distinctly control actions.
Asymmetric cortical projections to striatal direct and indirect pathways distinctly control actions.
复制标题
皮质对纹状体直接和间接通路的不对称投射明显控制着行为。
DOI：
10.1101/2023.10.02.560589
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Jin,Xin
中科院分区：
文献类型：
--
作者：
Klug,JasonR;Yan,Xunyi;Hoffman,HilaryA;Engelhardt,MaxD;Osakada,Fumitaka;Callaway,EdwardM;Jin,Xin
纹状体的直接和间接通路构成了基底神经节在行动控制中的核心功能。虽然纹状体D1和D2棘状投射神经元（SPN）都接受来自大脑皮层的兴奋性输入，但它们是否共享来自相同皮层神经元的输入，以及通路特异性皮质纹状体投射如何控制行为仍然是未知的。在这里，我们在小鼠中使用一种新的G缺失狂犬病系统，发现超过三分之二的D2-SPN兴奋性输入也靶向D1-SPN，而只有三分之一的D1-SPN兴奋性输入也靶向D2-SPN。纹状体D1与D2-SPN投射皮层神经元的光遗传刺激不同地调节运动，强化学习和序列行为，这意味着通路特异性皮质纹状体子回路的功能二分法。这些结果揭示了纹状体D1-与D2-SPN的部分隔离但不对称重叠的皮质投射，并且通路特异性皮质纹状体子回路明显控制行为。它在影响皮质基底神经节回路的广泛神经和精神疾病中具有重要意义。
The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a new G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do so vice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry.