Engstrom D A, Bickford P, De La Garza R, Young D, Rose G M
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Neurobiol Aging. 1993 May-Jun;14(3):259-66. doi: 10.1016/0197-4580(93)90010-9.
The effect of aging upon the responsiveness of hippocampal CA1 pyramidal neurons to nicotine was investigated using electrophysiological techniques in male Fischer 344 rats. Prior to electrophysiological recording, animals were behaviorally tested using the Morris water maze. All 3-6 and 18-21 month rats displayed rapid place learning in this task, while none of the 27-30 month animals learned within the 5-day test period. By contrast, rats of all age groups were able to learn a cue version of the water maze task. Following behavioral testing, the animals were anesthetized with sodium pentobarbital for acute recording. Nicotine was locally applied to electrophysiologically identified CA1 pyramidal neurons using pressure microejection from two-barreled glass microelectrodes. For each neuron, a dose of nicotine was found which elicited a 300-400% increase in basal firing rate. These data were used to construct cumulative dose response curves for populations of neurons tested in 3-6-, 18-21-, and 27-30-month-old animals. An age-related increase in the responsiveness of CA1 pyramidal neurons to locally applied nicotine was observed. The results of this study suggest that an increase in hippocampal CA1 pyramidal cell responsiveness to nicotine could be related to the impaired place learning ability seen with aging.
采用电生理技术，在雄性Fischer 344大鼠中研究衰老对海马CA1区锥体神经元对尼古丁反应性的影响。在进行电生理记录之前，使用Morris水迷宫对动物进行行为测试。所有3 - 6月龄和18 - 21月龄的大鼠在此任务中均表现出快速的位置学习能力，而27 - 30月龄的动物在5天的测试期内均未学会。相比之下，所有年龄组的大鼠都能够学会水迷宫任务的线索版本。行为测试后，用戊巴比妥钠麻醉动物以进行急性记录。使用双管玻璃微电极通过压力微喷射将尼古丁局部施加于电生理鉴定的CA1区锥体神经元。对于每个神经元，找到能使基础放电率增加300 - 400%的尼古丁剂量。这些数据用于构建3 - 6月龄、18 - 21月龄和27 - 30月龄动物测试的神经元群体的累积剂量反应曲线。观察到CA1区锥体神经元对局部施加尼古丁的反应性随年龄增长而增加。本研究结果表明，海马CA1区锥体细胞对尼古丁反应性的增加可能与衰老时出现的位置学习能力受损有关。
