TEMPORAL AND SPATIAL CHARACTERISTICS OF TONICALLY ACTIVE NEURONS OF THE PRIMATES STRIATUM
TEMPORAL AND SPATIAL CHARACTERISTICS OF TONICALLY ACTIVE NEURONS OF THE PRIMATES STRIATUM
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DOI：
10.1152/jn.1995.73.3.1234
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发表时间：
1995-03-01
影响因子：
2.5
通讯作者：
GRAYBIEL, AM
中科院分区：
文献类型：
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作者：
AOSAKI, T;KIMURA, M;GRAYBIEL, AM
1. 在经典条件反射任务的行为训练中，灵长类纹状体中的张力活跃神经元（TANs）对感觉条件反射刺激产生短暂反应。在这项研究中，我们研究了这种TAN反应的时间特征，并绘制了猕猴纹状体中响应听觉和视觉条件刺激的TAN的位置。我们进一步绘制了松鼠猴纹状体中敏锐记录的TAN的位置，与纹状体的神经化学区分的纹状体和基质室有关。并定量比较了组织化学和免疫组织化学染色鉴定的4种主要纹状体中间神经元与TANs的密度和区室分布。在听觉（咔嚓声）和视觉（发光二极管闪光）条件刺激的训练过程中，我们在不同时间对两只表现良好的猕猴纹状体不同部位的858个TANs进行了记录。分布在纹状体大部分区域的tan对条件刺激产生了反应，这些反应包括紧张性放电（暂停）的减少，随后是反弹兴奋，测量了单个tan的开始、抵消和暂停的持续时间以及相同细胞的峰间间隔（ISIs）。暂停反应的平均持续时间（268.3 ms）大于相同神经元的平均间隔时间（181 ms），表明暂停是对TAN放电的主动抑制。变异系数(CV！暂停反应的CV值为0.28，而相同细胞的ISIs的CV值为0.63。停顿的总体CV值为0.16，而ISIs的总体CV值为0.20。这些数据，再加上对反应的时间分析和人口直方图，表明在学习后，纹状体的大部分暂停在时间上是一致的。进行方差分析（ANOVAs）以确定在不同部位的TANs的暂停反应的开始和偏移潜伏期或暂停反应的持续时间是否存在差异。这些分析表明，除了极少数例外，在纹状体的大（bbb10毫米(3)）部分，TAN反应的时间没有差异。对纹状体不同区域的TAN反应的比较表明，对于给定条件刺激模式的反应，在尾状核或壳核中记录的TAN，以及在这些核的更前或更后部分记录的TAN，在暂停抵消时间上没有显著差异。唯一发现的区域差异是暂停发作时间，尾状核比壳核更早出现对视觉刺激的反应。对听觉和视觉条件刺激的反应比较表明，反应大体上是相似的，但点击的抵消时间和暂停时间比灯光的要长。在行为学习过程中不同时间记录的TAN反应的比较表明，TAN放电的主要差异是反应神经元数量的增加！从16.7%到62.0%)。此外，这些回应往往持续的时间稍长。反应性tan可以分为三类：只对听觉条件刺激有反应的tan，只对视觉条件刺激有反应的tan，以及对两者都有反应的tan。这些类型遇到的数量大致相等。不同类型的TANs没有明显聚集，但偶尔会发现有反应或无反应的细胞，或具有相同模式选择性的细胞。通过沉积芝加哥天蓝染料标记，对松鼠猴的82个TAN活性位点进行急性定位，随后对纹状体-基质区隔进行染色，发现有一半的TAN位点位于纹状体边界，如脑啡肽样肽免疫染色所定义的，或在这些边界的100 μ m范围内，其余的TAN位点全部位于边界以外的基质中。这些TAN分布值与纹状体（类似于16%）、纹状体周围100 μ m边缘（类似于8%）和基质以外（类似于76%）的比例面积估计值显著不同（P < 0.001）。松鼠猴纹状体中胆碱能神经元（胆碱乙酰转移酶免疫反应）、生长抑素能神经元（NADPH降酶阳性）、小白蛋白免疫反应强神经元和弱白蛋白免疫反应神经元的分布图表明，除了小白蛋白免疫反应神经元的弱染色亚群外，所有四种类型的中间神经元都具有在TAN图中发现的室室不对称的某些方面。生长抑素和calretinin中间神经元与TANs一样在纹状体中分化。除calretinin免疫反应性的中间神经元（和染色较弱的小白蛋白细胞）外，所有细胞在纹状体-基质边界上都有不同的浓度。不同神经元间类型的密度分布有明显差异。calretinin-immunoreactive and darkstained parvalbumin-immunoreactive neurons最多（65.3 cells/mm(2)）， 59.5 cells/mm(2))，生长抑素能神经元密度中等（29.2 cells/mm(2)），胆碱能中间神经元（10.1 cells/mm(2)）和弱染色的parvalbumin免疫反应细胞（7.9 cells/mm(2)）非常稀疏，一些神经元间分布在纹状体的一个或多个基本平面上显示出明显的密度梯度。对中间神经元分布的模拟记录分析表明，单电极穿透约可记录到12个胆碱能神经元、10个弱染色的小白蛋白神经元、54个生长抑素能神经元、80个暗染色的小白蛋白神经元、108个总小白蛋白神经元和113个calretinin神经元。在松鼠猴和猕猴中记录到的TANs密度为3-5个。因此，中间神经元的区室分布似乎排除了弱小蛋白阳性亚型作为电生理定义的TANs的可能候选表型，并且密度分布表明，在剩余的细胞类型中，胆碱能中间神经元最有可能与TANs相对应。TANs的强直性放电特性有力地支持了这一观点，因为在啮齿类动物中确定的胆碱能中间神经元在已知纹状体中间神经元中具有这种强直性活动是独一无二的。综上所述，灵长类纹状体中TANs的这些时空特征表明，在感觉运动学习过程中，这些神经元的反应在时间上是协调的。这些发现提出了一种可行的假设，即在感觉运动学习过程中，这种有条件的、时间协调的TANs活动可能参与了纹状体活动的重组机制。
1. Tonically active neurons (TANs) in the primate striatum develop transient responses to sensory conditioning stimuli during behavioral training in classical conditioning tasks. In this study we examined the temporal characteristics of such TAN responses and mapped the sites of TANs responding to auditory and visual conditioned stimuli in the striatum in macaque monkeys, We further mapped the locations of TANs recorded acutely in the squirrel monkey striatum in relation to the neurochemically distinguished striosome and matrix compartments of the striatum, and made quantitative comparisons between the densities and compartmental distributions of TANs and those of four major types of striatal interneuron identified by histochemical and immunohistochemical staining.2. We made recordings from 858 TANs at different sites in the striatum in two behaving macaque monkeys at different times during training with auditory (click) and visual (light-emitting diode flash) conditioning stimuli. TANs distributed across large parts of the striatum developed responses to the conditioning stimuli, The responses comprised a decrement of tonic Firing (pause) followed by a rebound excitation, Measurements were made of the onsets, offsets, and durations of the pauses of individual TANs and of the interspike intervals (ISIs) of the same cells.3. The mean duration of the pause responses (268.3 ms) was greater than the mean ISI of the same neurons (181 ms), suggesting that the pause represents on active suppression of TAN firing. The coefficient of variation (CV! for the pause responses was 0.28, compared with a CV of 0.63 for the same cells' ISIs. The population CV for the pauses was 0.16, compared with a population CV of 0.20 for the ISIs. These data, together with temporal analysis of the responses and population histograms, suggest that the pauses became temporally aligned across large parts of the striatum after ]earning. Analyses of variance (ANOVAs) were carried out to determine whether there were differences in the onset and offset latencies of the pause response or in the durations of the pause responses for TANs at different sites. These analyses suggested that, with rare exceptions, there was no difference in the timing of the TAN responses across large (>10 mm(3)) parts of the striatum.4. Comparisons of TAN responses in different regions of the striatum showed that, for responses to a given modality of conditioned stimulus, there were no significant differences in pause offset times for TANs recorded in the caudate nucleus or putamen, or for TANs recorded in more anterior or more posterior parts of these nuclei. The only regional difference found was for pause onset rimes, which were earlier in the caudate nucleus than in the putamen for the responses to visual stimuli. Comparisons of responses to auditory and visual conditioned stimuli showed that the responses were generally similar, but that the offset times and pause durations were greater for clicks than for lights.5. Comparisons of TAN responses recorded at different times during behavioral learning suggested that the main difference in TAN firing was an increase in the number of responsive neurons !from 16.7% to 62.0%). In addition, the responses tended to last slightly longer.6. Responsive TANs could be divided into three categories: those that responded only to the auditory conditioned stimuli, those that responded only to the visual conditioned stimuli, and those that responded to both. These types were encountered in roughly equal numbers. TANs of the different types were not obviously clustered, but runs of responders or nonresponders, or of cells sharing a modality selectivity profile, were occasionally found.7. Acute mapping of TANs in squirrel monkeys, made by depositing Chicago sky blue dye marks al 82 sites of TAN activity and subsequent staining for striosome-matrix compartmentation, showed that fully half of the TAN sites lay at striosomal borders, as defined by immunostaining For enkephalin-like peptide, or within similar to 100 mu m of those borders, The remaining TAN sites were ail in the matrix beyond the borders. These values for TAN distributions differed significantly (P < 0.001) from those estimated from the proportional areas For striosomes (similar to 16%), 100 mu m rims around striosomes (similar to 8%), and matrix beyond (similar to 76%).8. Distribution maps of cholinergic (choline acetyltransferase-immunoreactive), somatostatinergic (NADPH diaphorase-positive), strongly and weakly parvalbumin-immunoreactive, and calretinin-immunoreactive neurons in the squirrel monkey striatum established that, with the exception of the weakly stained subgroup of parvalbumin-immunoreactive neurons, all four types of interneuron shared some aspects of the compartmental asymmetries found in the TAN maps, The somatostatin and calretinin interneurons, like TANs, were rarified in striosomes. All but the calretinin-immunoreactive interneurons (and weakly stained parvalbumin cells) showed some differential concentration at striosome-matrix borders.9. There were sharply different density distributions for the different interneuronal types. The calretinin-immunoreactive and darkly stained parvalbumin-immunoreactive neurons were the most numerous (65.3 and 59.5 cells/mm(2)), somatostatinergic neurons were intermediate in density (29.2 cells/mm(2)), and the cholinergic interneurons (10.1 cells/mm(2)) and the weakly stained parvalbumin-immunoreactive cells (7.9 cells/mm(2)) were very sparse, Some of the interneuronal distributions showed marked gradients in density across one or more of the cardinal planes of the striatum.10. Simulation recording analysis of the interneuron distributions suggested that, in a single electrode penetration, approximately 12 cholinergic neurons, 10 weakly stained parvalbumin neurons, 54 somatostatinergic neurons, 80 darkly stained parvalbumin neurons, 108 total parvalbumin neurons, and 113 calretinin neurons would be recorded. The TANs actually recorded in the squirrel monkeys and macaque monkeys were found at a density of 3-5 in a penetration. Thus the compartmental distributions of the interneurons appeared to exclude the weakly parvalbumin-positive subtype as a probable candidate phenotype for the electrophysiologically defined TANs, and the density distributions suggested that of the remaining cell types, the cholinergic interneurons are most likely to correspond to the TANs. The tonic firing property of the TANs strongly supports this view, because the cholinergic interneurons definitively identified in rodents are unique among known striatal interneurons in having such tonic activity.11. These temporospatial characteristics of TANs in the primate striatum, taken together, suggest that the responses of these neurons become temporally coordinated during sensorimotor learning. A working hypothesis suggested by these findings is that such conditioned, temporally coordinated activity of the TANs could participate in mechanisms reorganizing striatal activity during sensorimotor learning.