Abstract:
Neuromodulation such as deep brain stimulation (DBS) is advancing as a clinical intervention in several neurological and neuropsychiatric disorders, including Parkinson\'s disease, dystonia, tremor, and obsessive-compulsive disorder (OCD) for which DBS is already applied to alleviate severely afflicted individuals of symptoms. Tourette syndrome and drug addiction are two additional disorders for which DBS is in trial or proposed as treatment. However, some major remaining obstacles prevent this intervention from reaching its full therapeutic potential. Side-effects have been reported, and not all DBS-treated individuals are relieved of their symptoms. One major target area for DBS electrodes is the subthalamic nucleus (STN) which plays important roles in motor, affective and associative functions, with impact on for example movement, motivation, impulsivity, compulsivity, as well as both reward and aversion. The multifunctionality of the STN is complex. Decoding the anatomical-functional organization of the STN could enhance strategic targeting in human patients. The STN is located in close proximity to zona incerta (ZI) and the para-subthalamic nucleus (pSTN). Together, the STN, pSTN and ZI form a highly heterogeneous and clinically important brain area. Rodent-based experimental studies, including opto- and chemogenetics as well as viral-genetic tract tracings, provide unique insight into complex neuronal circuitries and their impact on behavior with high spatial and temporal precision. This research field has advanced tremendously over the past few years. Here, we provide an inclusive review of current literature in the pre-clinical research fields centered around STN, pSTN and ZI in laboratory mice and rats; the three highly heterogeneous and enigmatic structures brought together in the context of relevance for treatment strategies. Specific emphasis is placed on methods of manipulation and behavioral impact.
摘要:
诸如深部脑刺激(DBS)之类的神经调节正在作为几种神经和神经精神疾病的临床干预措施而发展。包括帕金森病,肌张力障碍,震颤,和强迫症(OCD),DBS已经用于减轻严重患病的个体的症状。Tourette综合征和药物成瘾是DBS正在试验或建议治疗的两种其他疾病。然而,一些仍然存在的主要障碍阻碍了这种干预措施达到其全部治疗潜力。据报道有副作用,并非所有接受DBS治疗的患者都能缓解症状。DBS电极的一个主要目标区域是丘脑底核(STN),在运动中起着重要作用,情感和联想功能,例如对运动的影响,动机,冲动,强迫性,以及奖励和厌恶。STN的多功能性是复杂的。解码STN的解剖功能组织可以增强人类患者的战略靶向性。STN位于紧靠不透明带(ZI)和对丘脑核(pSTN)的位置。一起,STN,pSTN和ZI形成高度异质和临床重要的脑区域。基于啮齿动物的实验研究,包括光遗传学和化学遗传学以及病毒遗传道,提供对复杂的神经元电路及其对具有高空间和时间精度的行为的影响的独特见解。在过去的几年里,这一研究领域取得了巨大的进步。这里,我们提供了以STN为中心的临床前研究领域的现有文献的包容性综述,实验室小鼠和大鼠中的pSTN和ZI;在与治疗策略相关的背景下,这三个高度异质和神秘的结构汇集在一起。特别强调操纵和行为影响的方法。