Nanda Bijli, Galvan Adriana, Smith Yoland, Wichmann Thomas
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Eur J Neurosci. 2009 Feb;29(3):588-98. doi: 10.1111/j.1460-9568.2008.06598.x. Epub 2009 Jan 17.
Although the existence of a massive projection from the caudal intralaminar nuclei of the thalamus [i.e. the centromedian (CM) and parafascicular nuclei] to the striatum is well documented, the effects of CM activation upon striatal cells remain poorly understood. Therefore, we studied the effects of electrical stimulation of CM on the electrophysiological activity of striatal neurons, and on striatal levels of gamma-aminobutyric acid (GABA) and acetylcholine in rhesus monkeys. Striatal cells did not respond to single-pulse stimulation (bipolar biphasic stimulation, 175-500 muA), but the large majority of recorded neurons responded to burst stimulation (100 Hz, 1 s, 150-175 muA) of CM, often with a delay of tens of milliseconds. Striatal phasically active neurons, which likely correspond to projection neurons, responded mainly with increases in firing (13/28 cells), while tonically active neurons (likely cholinergic interneurons) often showed combinations of increases and decreases in firing (24/46 cells). In microdialysis studies, CM stimulation led to a reduction of striatal acetylcholine levels. This effect was prevented by addition of the GABA-A receptor antagonist gabazine to the microdialysis fluid. We conclude that CM stimulation frequently results in striatal response patterns with excitatory and inhibitory components. Under the conditions chosen here, the specific patterns of striatal responses to CM stimulation are likely the result of striatal processing of thalamic inputs. Through these indirect effects, local CM stimulation may engage large portions of the striatum. These effects may be relevant in the interpretation of the therapeutic effects of CM stimulation for the treatment of neurological disorders.
虽然丘脑尾侧内核层[即中央中核(CM)和束旁核]向纹状体发出大量投射这一现象已有充分记录,但CM激活对纹状体细胞的影响仍知之甚少。因此,我们研究了电刺激CM对恒河猴纹状体神经元电生理活动以及纹状体中γ-氨基丁酸(GABA)和乙酰胆碱水平的影响。纹状体细胞对单脉冲刺激(双极双相刺激,175 - 500 μA)无反应,但绝大多数记录到的神经元对CM的阵发刺激(100 Hz,1 s,150 - 175 μA)有反应,通常有几十毫秒的延迟。纹状体相位性活动神经元可能对应于投射神经元,主要表现为放电增加(13/28个细胞),而紧张性活动神经元(可能是胆碱能中间神经元)常常表现出放电增加和减少的组合(24/46个细胞)。在微透析研究中,CM刺激导致纹状体乙酰胆碱水平降低。向微透析液中添加GABA - A受体拮抗剂加巴喷丁可防止这种效应。我们得出结论,CM刺激经常导致纹状体出现具有兴奋和抑制成分的反应模式。在本文所选用的条件下,纹状体对CM刺激的特定反应模式可能是丘脑输入在纹状体中进行处理的结果。通过这些间接效应,局部CM刺激可能会使纹状体的大部分区域参与其中。这些效应可能与解释CM刺激对神经系统疾病治疗的疗效有关。