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双Y迷宫中的记忆缺陷与向大鼠基底核注射鹅膏蕈氨酸和喹啉酸对杏仁核中胆碱乙酰转移酶的影响有关。

Mnemonic deficits in the double Y-maze are related to the effects of nucleus basalis injections of ibotenic and quisqualic acid on choline acetyltransferase in the rat amygdala.

作者信息

Beninger R J, Kühnemann S, Ingles J L, Jhamandas K, Boegman R J

机构信息

Department of Psychology, Queen's University, Kingston, Ontario, Canada.

出版信息

Brain Res Bull. 1994;35(2):147-52. doi: 10.1016/0361-9230(94)90095-7.

Abstract

Many researchers have reported that the magnitude of decrease in cortical choline acetyltransferase (ChAT) following excitotoxic lesions of the nucleus basalis magnocellularis (nbm) is unrelated to the degree of cognitive impairment. Recently, an explanation has been offered for this lack of correlation: different excitotoxins, when injected into the nbm, differentially affected cholinergic projections to the cortex and amygdala, and those excitotoxins previously reported to produce the greatest mnemonic deficits produced the largest decreases in amygdaloid ChAT. The present study evaluated the role of amygdalofugal cholinergic projections in memory by comparing the effects of intra-nbm ibotenic and quisqualic acid on cortical and amygdaloid ChAT and on mnemonic performance in the double Y-maze. Rats were trained in the double Y-maze until working and reference memory choice accuracy stabilized to a criterion of > or = 78% correct. Rats then were given either bilateral quisqualic acid (60 nmol in 0.5 microliter), bilateral ibotenic acid (50 nmol in 0.5 microliter), or sham (0.9% saline in 0.5 microliter) lesions of the nbm, and again were tested on the maze. Quisqualate produced a selective impairment of working memory, a large (51%) decrease in cortical ChAT and a small (17%) decrease in amygdaloid ChAT; ibotenate, on the other hand, produced a greater impairment of working memory, an impairment of reference memory, a similar (51%) decrease in cortical ChAT, but a greater (30%) decrease in amygdaloid ChAT. These results suggest that the cholinergic projections from the nbm to the cortex and amygdala play an important role in memory. They suggest that excitotoxins producing greater depletions of amygdaloid ChAT produce greater mnemonic deficits.

摘要

许多研究人员报告称,在基底大细胞核(nbm)发生兴奋性毒性损伤后,皮质胆碱乙酰转移酶(ChAT)的下降幅度与认知障碍程度无关。最近,有人对这种缺乏相关性的现象给出了解释:不同的兴奋性毒素注入nbm后,对投射到皮质和杏仁核的胆碱能神经通路产生的影响各不相同,而且先前报道的那些能导致最大记忆缺陷的兴奋性毒素会使杏仁核ChAT下降幅度最大。本研究通过比较向nbm内注射鹅膏蕈氨酸和喹啉酸对皮质和杏仁核ChAT以及对双Y迷宫中记忆表现的影响,评估了杏仁核传出胆碱能神经通路在记忆中的作用。将大鼠在双Y迷宫中进行训练,直到工作记忆和参考记忆的选择准确率稳定在≥78%正确的标准。然后,给大鼠进行nbm的双侧喹啉酸(60纳摩尔溶于0.5微升)、双侧鹅膏蕈氨酸(50纳摩尔溶于0.5微升)或假手术(0.9%生理盐水0.5微升)损伤,之后再次在迷宫中进行测试。喹啉酸导致工作记忆选择性受损、皮质ChAT大幅下降(51%)以及杏仁核ChAT小幅下降(17%);另一方面,鹅膏蕈氨酸导致工作记忆受损更严重、参考记忆受损、皮质ChAT下降幅度类似(51%),但杏仁核ChAT下降幅度更大(30%)。这些结果表明,从nbm投射到皮质和杏仁核的胆碱能神经通路在记忆中起重要作用。结果表明,导致杏仁核ChAT耗竭更严重的兴奋性毒素会产生更严重的记忆缺陷。

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