Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.
Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.
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DOI：
10.1016/j.neuroimage.2015.12.056
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发表时间：
2016-03
期刊：
影响因子：
5.7
通讯作者：
Lee KH
中科院分区：
文献类型：
--
作者：
Ross EK;Kim JP;Settell ML;Han SR;Blaha CD;Min HK;Lee KH
脑深部刺激(DBS)是一种基于电路的治疗方法，可缓解多种神经和神经精神疾病的症状。为了治疗与阿尔茨海默病(AD)相关的记忆障碍，几项临床试验已经测试了穹隆附近DBS的疗效。这些研究的早期结果表明，接受穹隆DBS治疗的患者在记忆力和生活质量方面都有改善，但这种效果背后的机制仍然存在争议。众所周知，内侧边缘和皮质边缘回路之间的传递在陈述性记忆中起着不可或缺的作用，而回路水平的功能障碍会导致包括AD在内的各种形式的痴呆。在这里，我们的目的是通过研究穹隆DBS参与的功能回路和脑结构来确定穹隆DBS的潜在潜在机制。采用多模式方法研究了麻醉猪穹窿DBS模型中发生的整体和局部时间变化。用功能磁共振成像(FMRI)检测穹隆电刺激时整体功能活动的变化，用快速扫描循环伏安法(FSCV)监测局部神经化学变化。此外，还进行了伏隔核(NAC)的颅内微量注射，以研究多巴胺和谷氨酸受体特异性拮抗作用对整体活动的影响。用fMRI检测穹隆DBS引起的内侧边缘和皮质边缘环的血流动力学反应。此外，穹隆DBS导致NAC内FSCV监测的多巴胺氧化电流(对应于多巴胺外流)增加。最后，NAC的多巴胺和谷氨酸受体拮抗后，穹隆DBS在杏仁核和海马区引起的血流动力学反应减弱。本研究结果提示，穹隆DBS通过兴奋性谷氨酸能输入调节NAc内突触前多巴胺能终末的多巴胺释放，内侧边缘和皮质边缘环路在功能环路中相互作用。
Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop.