Subthalamic neurons coordinate basal ganglia function through differential neural pathways
Subthalamic neurons coordinate basal ganglia function through differential neural pathways
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DOI：
10.1523/jneurosci.1904-05.2005
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发表时间：
2005-08-24
影响因子：
5.3
通讯作者：
Kobayashi, K
中科院分区：
文献类型：
--
作者：
Yasoshima, Y;Kai, N;Kobayashi, K
丘脑底核(STN)是调节多种运动功能的基础神经节回路的重要组成部分。STN神经元将谷氨酸能投射投射到基底节的输出结构，包括黑质网状部(SNR)和内侧丘脑核，也支配苍白球(GP)。然而，STN调节神经回路中运动功能的机制尚不完全清楚。在这里，我们使用免疫毒素介导的细胞靶向对STN神经元进行有条件的消融。然后我们分析了多巴胺(DA)介导的运动行为和SNR和GP神经元的放电活动。消融STN神经元可增加自发活动，减少对DA刺激的过度活动。消融这些神经元调制了SNR神经元的自发放电模式和频率，但对GP神经元的自发放电没有实质性影响。消融可减弱DA引起的SNR神经元放电频率的抑制，并抑制DA引起的GP神经元放电频率的升高。此外，药物阻断对DA刺激反应的GP激活可抑制SNR活性和由此产生的运动激活。这些结果表明，STN神经元通过直接投射到输出神经元来抑制自发行为，而作为对DA的反应，它们主要通过GP介导的通路作用于输出神经元，从而促进行为的表达。我们得出结论，视DA传递状态而定，STN通过不同的神经通路来协调运动行为。
The subthalamic nucleus (STN) is a key component of basal ganglia circuitry that mediates a variety of motor functions. The STN neurons send glutamatergic projections to the output structures of basal ganglia, including the substantia nigra pars reticulata (SNr) and the entopeduncular nucleus, and also innervate the globus pallidus ( GP). However, the mechanism by which the STN regulates motor functions in the neural circuitry is not fully understood. Here we performed conditional ablation of the STN neurons by using immunotoxin-mediated cell targeting. We then analyzed dopamine (DA)-mediated motor behavior and firing activity of the SNr and GP neurons. Ablation of the STN neurons increased spontaneous movement and reduced hyperactivity in response to DA stimulation. Ablation of these neurons modulated the pattern and rate of spontaneous firing of the SNr neurons, although it did not substantially affect spontaneous firing of the GP neurons. The ablation attenuated DA-induced suppression of the firing rate of the SNr neurons and inhibited DA-induced elevation of the rate of the GP neurons. In addition, pharmacological blockade of GP activation in response to DA stimulation inhibited the suppression of SNr activity and the resultant motor activation. These results suggest that the STN neurons suppress spontaneous behavior through their direct projection to the output neurons and that, in response to DA, they contribute to expression of behavior by acting on the output neurons mainly through the GP-mediated pathways. We conclude that the STN coordinates motor behavior through differential neural pathways depending on the state of DA transmission.