Van der Zee E A, Douma B R, Bohus B, Luiten P G
Department of Animal Physiology, University of Groningen, The Netherlands.
Cereb Cortex. 1994 Jul-Aug;4(4):376-90. doi: 10.1093/cercor/4.4.376.
Changes in neocortical immunoreactivity (ir) for muscarinic acetylcholine receptors (mAChRs), protein kinase C gamma (PKC gamma), microtubule-associated protein 2 (MAP-2), and the calcium-binding protein parvalbumin (PARV) induced by the performance of a one-trial passive shock avoidance (PSA) task were studied in young adult male Wistar rats. In experiment I, four groups of animals were formed: three control groups (N, naive; H, habituated but nonshocked; and S, habituated and shocked), and a fully trained group (T, habituated and shocked, followed by a retention trial 24 hr after the footshock). Compared to naive animals, the H, S, and T animals all revealed enhanced cortical ir for mAChRs, PKC gamma, and MAP-2 in discrete subsets of cortical neurons in layers 2, 3, and 5, while no changes were found for PARV. The neurons displaying enhanced levels of ir are of the pyramidal and nonpyramidal cell type and are arranged in a columnar manner. Immunofluorescent double-labeling experiments for mAChR, PKC gamma, and MAP-2 revealed that individual cortical neurons localized within the columns display enhanced ir for all three functionally related proteins. Compared to naive animals, all experimental groups revealed significant increases in the total size of cortical areas showing enhanced ir (H, S, and T over N). A further significant increase is found in animals receiving a footshock over nonshocked animals (S over H, respectively). The retention trial, however, did not induce a further increase (T over S). In some of the animals the patterns appeared to be lateralized, in either the left or right hemisphere. In order to test the role of cholinergic innervation in the induction of enhanced mAChR-ir, unilateral lesions of the nucleus basalis magnocellularis (nbm) were performed in experiment II. Apparently, an intact cholinergic innervation from the nbm is not required for the occurrence of the aforementioned columnar patterns. However, when the enhanced columnar patterns in the sensory areas of the cortex are cholinergically deprived, clear deficits in PSA performance are observed. These results indicate that although ACh is not a prerequisite for the induction of enhanced ir for mAChRs in cortical cells, such neurons demand cholinergic neurotransmission for optimal retention of the shock experience. The alterations in ir for coexpressed mAChR, PKC gamma, and MAP-2 in a discrete subset of cholinoceptive cortical neurons arranged in characteristic patterns most likely represent part of the neuronal substrate involved in functional cortical plasticity related to PSA training.
在年轻成年雄性Wistar大鼠中，研究了单次被动回避电击（PSA）任务的执行所诱导的新皮质中毒蕈碱型乙酰胆碱受体（mAChRs）、蛋白激酶Cγ（PKCγ）、微管相关蛋白2（MAP - 2）和钙结合蛋白小白蛋白（PARV）免疫反应性（ir）的变化。在实验I中，形成了四组动物：三个对照组（N，未处理组；H，习惯化但未电击组；S，习惯化且电击组），以及一个完全训练组（T，习惯化且电击组，在足部电击后24小时进行一次保留试验）。与未处理动物相比，H、S和T组动物在第2、3和5层皮质神经元的离散亚群中，mAChRs、PKCγ和MAP - 2的皮质ir均增强，而PARV未发现变化。显示ir水平增强的神经元为锥体细胞和非锥体细胞类型，并呈柱状排列。对mAChR、PKCγ和MAP - 2进行免疫荧光双标记实验表明，位于柱内的单个皮质神经元对所有三种功能相关蛋白的ir均增强。与未处理动物相比，所有实验组显示ir增强的皮质区域总面积均显著增加（H、S和T组相对于N组）。在接受电击的动物中比未电击动物有进一步显著增加（S组相对于H组）。然而，保留试验并未诱导进一步增加（T组相对于S组）。在一些动物中，这些模式似乎在左半球或右半球出现偏侧化。为了测试胆碱能神经支配在诱导增强的mAChR - ir中的作用，在实验II中对基底大细胞核（nbm）进行了单侧损伤。显然，上述柱状模式的出现并不需要来自nbm的完整胆碱能神经支配。然而，当皮质感觉区域中增强的柱状模式被胆碱能剥夺时，在PSA表现中观察到明显的缺陷。这些结果表明，虽然乙酰胆碱不是诱导皮质细胞中mAChRs的ir增强的先决条件，但此类神经元需要胆碱能神经传递以最佳保留电击经历。以特征性模式排列的胆碱能感受性皮质神经元离散亚群中，共表达的mAChR、PKCγ和MAP - 2的ir变化很可能代表了与PSA训练相关的功能性皮质可塑性所涉及的神经元底物的一部分。
