Risbrough Victoria, Bontempi Bruno, Menzaghi Frédérique
Department of Neuroscience-0804, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Psychopharmacology (Berl). 2002 Oct;164(1):71-81. doi: 10.1007/s00213-002-1170-7. Epub 2002 Aug 9.
Excitotoxic lesions of the nucleus basalis magnocellularis (nbm) in rats produce deficits in performance of the 5-choice serial reaction time (5CSRT) task, suggesting that basal forebrain cholinergic projections to the neocortex play an important role in visuospatial attention. However, non-selective damage induced by excitotoxins may have confounded the interpretation of the specific contribution of the corticopetal cholinergic neurons of the nbm to attentional processes.
The purpose of the present study was to produce selective immunolesions of the cholinergic neurons of the nbm in order to examine more precisely the role of the cholinergic projections of the basal forebrain on attentional performance in a 5CSRT task.
Rats received bilateral injections of the selective cholinergic immunotoxin 192 IgG-saporin (0.067 microg/ microl, 1 microl) into the nbm after baseline training in the 5CSRT task. Performance of sham and nbm lesion groups was then assessed during baseline and increased task difficulty conditions.
Contrary to results previously reported, accuracy of responding and behavioral inhibition were unaffected by the immunotoxin. Rats with nbm lesions showed, however, significant increases in omissions relative to control rats, most markedly during sessions with increased difficulty of signal detection, e.g., decreased stimulus intensity or duration. Magazine and correct latencies were unaffected, suggesting that the lesion-induced omissions were not due to changes in motivation. Omissions were highly correlated with percentage of choline acetylcholine transferase depletion. Reduced premature responses were also observed when the target stimulus was made less predictable.
Although the 192 IgG-saporin lesion produced a different array of behavioral deficits than previously reported, these effects nevertheless are consistent with an important role of the basal forebrain cholinergic system in attentional function, in particular with accurate timing of stimulus presentation and target detection.
大鼠基底大细胞核（nbm）的兴奋性毒性损伤会导致其在5选串行反应时（5CSRT）任务中的表现出现缺陷，这表明基底前脑向新皮层的胆碱能投射在视觉空间注意力方面发挥着重要作用。然而，兴奋性毒素引起的非选择性损伤可能混淆了对nbm向皮层投射的胆碱能神经元对注意力过程具体贡献的解释。
本研究的目的是对nbm的胆碱能神经元进行选择性免疫损伤，以便更精确地研究基底前脑胆碱能投射在5CSRT任务中对注意力表现的作用。
在5CSRT任务的基线训练后，给大鼠双侧注射选择性胆碱能免疫毒素192 IgG-皂草素（0.067微克/微升，1微升）到nbm。然后在基线和任务难度增加的条件下评估假手术组和nbm损伤组的表现。
与先前报道的结果相反，免疫毒素并未影响反应准确性和行为抑制。然而，与对照大鼠相比，nbm损伤的大鼠遗漏显著增加，在信号检测难度增加的实验中最为明显，例如刺激强度或持续时间降低时。食丸潜伏期和正确潜伏期未受影响，这表明损伤引起的遗漏并非由于动机变化。遗漏与胆碱乙酰转移酶耗竭百分比高度相关。当目标刺激的可预测性降低时，还观察到过早反应减少。
尽管192 IgG-皂草素损伤产生了与先前报道不同的一系列行为缺陷，但这些效应仍与基底前脑胆碱能系统在注意力功能中的重要作用一致，特别是在刺激呈现和目标检测的精确计时方面。
