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腹侧苍白球/无名质神经元的多巴胺电生理学:与背侧苍白球的比较。

Dopamine electrophysiology of ventral pallidal/substantia innominata neurons: comparison with the dorsal globus pallidus.

作者信息

Napier T C, Simson P E, Givens B S

机构信息

Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois.

出版信息

J Pharmacol Exp Ther. 1991 Jul 1;258(1):249-62.

PMID:1677041
Abstract

The ventral pallidum/substantia innominata (VP/SI) is an infracommissural extension of the dorsal globus pallidus (GP). Functional studies suggest that the VP/SI is indirectly influenced by dopamine (DA) via inputs from dopaminoceptive regions. However, recent anatomical evidence indicates a direct dopaminergic projection to the VP/SI, but the physiologic and pharmacologic consequences of this input have not been evaluated. Thus, the present study was designed to electrophysiologically characterize VP/SI neuronal responses to i.v. administered apomorphine (APO) and microiontophoretically applied DA. Because of similarities in circuitry and morphology, VP/SI responses were compared to those obtained from the GP. Single neurons recorded in vivo from rat VP/SI and GP exhibited similar electrophysiologic characteristics. The majority of the 50 neurons tested with APO demonstrated a dose-related increase in firing rate, with equivalent maximum responses and equivalent doses that produced half-maximal responding (ED50) for the two brain areas. APO generally was antagonized by haloperidol, indicating that the agonist was acting at dopaminergic receptors to produce the observed rate changes. From 212 neurons tested, it was determined that microiontophoretically applied DA altered neuronal firing throughout both regions. However, more DA-sensitive neurons were encountered in the GP than the VP/SI (75% vs. 42%, respectively). DA-induced rate increases and decreases were observed, with rate suppression occurring most frequently. The maximum response and the current that produced half-maximal responding were comparable for the two regions for both response directions. Systemic administration of antagonists revealed that pallidal responses to dopamine likely involve both the D1 and D2 receptor subtypes. These studies 1) demonstrate that the VP/SI is a functionally important dopaminoceptive brain region, and (2) confirm previous work regarding dopaminergic regulation of the GP. The similarities in pharmacologic profiles of responses by GP and VP/SI neurons to dopaminergic agents likely reflect comparable circuitries for the two regions. The differential responding to systemically administered DA agonists and locally applied DA implies that a combination of direct and indirect influences ultimately determines the impact that an activated dopaminergic system has on pallidal brain regions.

摘要

腹侧苍白球/无名质(VP/SI)是背侧苍白球(GP)在连合下的延伸部分。功能研究表明,VP/SI通过来自多巴胺感受区域的输入间接受到多巴胺(DA)的影响。然而,最近的解剖学证据表明存在一条直接的多巴胺能投射至VP/SI,但该输入的生理和药理学后果尚未得到评估。因此,本研究旨在通过电生理学方法表征VP/SI神经元对静脉注射阿扑吗啡(APO)和微量离子透入法应用多巴胺的反应。由于在神经回路和形态上的相似性,将VP/SI的反应与从GP获得的反应进行了比较。在大鼠VP/SI和GP中体内记录的单个神经元表现出相似的电生理特征。用APO测试的50个神经元中的大多数显示出与剂量相关的放电率增加,两个脑区的最大反应和产生半数最大反应的等效剂量(ED50)相当。APO通常被氟哌啶醇拮抗,表明该激动剂作用于多巴胺能受体以产生观察到的放电率变化。在测试的212个神经元中,确定微量离子透入法应用的多巴胺改变了两个区域的神经元放电。然而,在GP中遇到的对多巴胺敏感的神经元比VP/SI中更多(分别为75%和42%)。观察到多巴胺诱导的放电率增加和减少,其中放电率抑制最为常见。两个区域在两个反应方向上产生半数最大反应的最大反应和电流相当。拮抗剂的全身给药表明,苍白球对多巴胺的反应可能涉及D1和D2受体亚型。这些研究1)表明VP/SI是一个功能上重要的多巴胺感受性脑区,并且(2)证实了先前关于GP多巴胺能调节的工作。GP和VP/SI神经元对多巴胺能药物反应的药理学特征相似,这可能反映了两个区域具有可比的神经回路。对全身给予的多巴胺激动剂和局部应用的多巴胺的不同反应意味着直接和间接影响的组合最终决定了激活的多巴胺能系统对苍白球脑区的影响。

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