Gale John T, Lee Kendall H, Amirnovin Ramin, Roberts David W, Williams Ziv M, Blaha Charles D, Eskandar Emad N
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA.
Stereotact Funct Neurosurg. 2013;91(6):355-63. doi: 10.1159/000351523. Epub 2013 Oct 9.
Primate studies demonstrate that high-frequency electrical stimulation (HFS) of the caudate can enhance learning. Importantly, in these studies, stimulation was applied following the execution of behavior and the effect persisted into subsequent trials, suggesting a change in plasticity rather than a momentary facilitation of behavior.
OBJECTIVES/METHODS: Although the mechanism of HFS-enhanced learning is not understood, evidence suggests that dopamine plays a critical role. Therefore, we used in vivo amperometry to evaluate the effects of HFS on striatal dopamine release in the anesthetized primate. While this does not directly examine dopamine during learning, it provides insight with relation to dopamine dynamics during electrical stimulation and specifically between different stimulation parameters and striatal compartments.
We demonstrate that HFS results in significantly more dopamine release in the striatum compared to low-frequency stimulation. In addition, electrical stimulation operates differentially on specific neuronal elements, as the parameters for dopamine release are different for the caudate, putamen and medial forebrain bundle.
While not direct evidence, these data suggest that HFS evokes significant dopamine release which may play a role in stimulation-enhanced learning. Moreover, these data suggest a means to modulate extracellular dopamine with a high degree of temporal and spatial precision for either research or clinical applications.
灵长类动物研究表明，对尾状核进行高频电刺激（HFS）可增强学习能力。重要的是，在这些研究中，刺激是在行为执行后施加的，且这种效果持续到后续试验中，这表明可塑性发生了变化，而非行为的瞬间促进。
目的/方法：尽管HFS增强学习的机制尚不清楚，但有证据表明多巴胺起着关键作用。因此，我们采用体内安培测量法来评估HFS对麻醉灵长类动物纹状体多巴胺释放的影响。虽然这并不能直接检测学习过程中的多巴胺，但它能提供有关电刺激期间多巴胺动态变化的见解，特别是不同刺激参数与纹状体不同区域之间的关系。
我们证明，与低频刺激相比，HFS导致纹状体中多巴胺释放显著增加。此外，电刺激对特定神经元成分的作用存在差异，因为尾状核、壳核和内侧前脑束的多巴胺释放参数不同。
虽然不是直接证据，但这些数据表明HFS引发显著的多巴胺释放，这可能在刺激增强学习中发挥作用。此外，这些数据提示了一种手段，可为研究或临床应用以高度的时间和空间精度调节细胞外多巴胺。
