Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032, USA.
Nat Commun. 2023 Oct 23;14(1):6712. doi: 10.1038/s41467-023-42288-1.
In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.
在基底神经节的经典模型中，直接通路纹状体投射神经元（dSPNs）向黑质（SNr）和被盖核投射，以调节运动功能。最近的研究重新确立了 dSPNs 也在苍白球内（GPe）具有轴突侧支（桥接侧支），但这些侧支对行为的意义尚不清楚。在这里，我们使用活体光学和化学遗传学工具以及小鼠中的深度学习方法来剖析 dSPN GPe 侧支在运动功能中的作用。我们发现，投射到 SNr 的 dSPNs 通过轴突侧支向 GPe 发送同步的与运动相关的信息。抑制 dSPN GPe 末梢的内源性活性通过调节 Npas1 神经元来损害运动活动和功能。我们提出了一个模型，即 dSPN GPe 轴突侧支（纹状体苍白球 Go 通路）与 SNr 中的典型末梢协同作用，通过抑制 Npas1 神经元来支持运动控制。
