Lidia Miguel Telega, Danesh Ashouri Vajari, Chockalingam Ramanathan, Volker A Coenen, Máté D Döbrössy
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引用次数: 0
摘要
内侧前脑束深部脑刺激(MFB-DBS)可对治疗耐受性抑郁症(TRD)患者产生快速而持久的抗抑郁效果。其机制尚不十分清楚,但有一种假设认为,多巴胺能(DAergic)纤维的调节有助于治疗效果。已经研究了急性 DBS 对 DA 释放的影响,但还缺乏急性重复性 DBS 的纵向研究。在对行为动物和非行为动物进行急性和重复性刺激后的 8 周内,我们使用纤维光度计测量了 Long-Evans accumbal DA 释放和腹侧被盖区(VTA)钙离子对不同 mfb-DBS 参数的强直性和相位性信号传导。随着频率和 DBS 持续时间的增加,在两个目标中都观察到了 DBS 诱导的释放。随着时间的推移,130 Hz 刺激会增加相性和强直性 DA 反应,后者是其长期临床有效性的潜在机制。VTA钙离子瞬时降低,而相性活动随频率增加而增加。脉宽(PW)介导的峰值释放时间差异也表明,它可能会平行激活不同的纤维类型。此外,在高架迷宫(EPM)过程中,DA瞬时率的降低表明DA的释放与环境和刺激持续时间有关。这些数据证实了慢性反向/正向 DAergic 反应与刺激参数相关的可变性,为 mfb DBS 的时间适应性、连接性和纤维招募提供了新的见解。
Chronic in vivo sequelae of repetitive acute mfb-DBS on accumbal dopamine and midbrain neuronal activity.
Medial Forebrain Bundle Deep Brain Stimulation (MFB-DBS) can have rapid and long lasting antidepressant effects in Treatment Resistant Depression (TRD) patients. The mechanisms are not well understood, but one hypothesis stipulates that modulation of the dopaminergic (DAergic) fibers contribute to the therapeutic outcome. Acute DBS effects on DA release have been studied; however, longitudinal studies with acute-repetitive DBS are lacking. Long-Evans accumbal DA release and Ventral Tegmental Area (VTA) calcium tonic and phasic signaling to different mfb-DBS parameters were measured using fiber photometry over 8 weeks, following acute and repetitive stimulation in behaving and non-behaving animals. DBS-induced release was observed in both targets, with increased frequency and DBS duration. 130 Hz stimulation increased phasic and tonic DA response over time, with the latter being a potential mechanism for its long-term clinical effectiveness. VTA calcium transients decreased, while phasic activity increased with frequency. Pulse width (PW)-mediated differential peak release timing also suggests potential parallel activation of diverse fiber types. Additionally, decreased DA transients rate during Elevated Plus Maze (EPM) suggests context and stimulation duration-dependent DA release. The data confirm chronic antidromic/orthodromic DAergic responses with stimulation parameter dependent variability, providing novel insights into temporal adaptations, connectivity and fiber recruitment on mfb DBS.
期刊介绍:
Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.