Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tübingen, Germany.
Magn Reson Imaging. 2010 Oct;28(8):1165-74. doi: 10.1016/j.mri.2009.12.022. Epub 2010 Jan 21.
Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn(2+) is a metabolic toxin and a competitive inhibitor for Ca(2+), and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl(2) administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl(2), respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl(2) dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca(2+) competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl(2). Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl(2) may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn(2+) administration protocol.
锰（Mn(2+)）增强磁共振成像（MEMRI）提供了在不受约束和行为动物中生成脑活动纵向图谱的可能性。然而，Mn(2+)是一种代谢毒素和 Ca(2+)的竞争性抑制剂，因此，MEMRI 研究中的一个尚未解决的问题是，所使用的金属离子浓度是否会改变脑生理学。在本工作中，我们研究了 MnCl(2)在 MEMRI 中经常使用的浓度和剂量方案下给药的行为、电生理和组织病理学后果。三组动物分别用生理盐水、0.1 和 0.5 mmol/kg MnCl(2)sc 注射。在海马结构中的体内电生理记录显示，在最高 MnCl(2)剂量下，兴奋性突触后电位（EPSP）和群体锋电位（PS）幅度都出现了轻微但可检测的降低。EPSP 与 PS 的比值保持在对照水平，表明神经元兴奋性未受影响。双脉冲易化实验表明，第二脉冲的增强与剂量呈依赖性增加，表明神经元反应降低的机制是突触前 Ca(2+)竞争。穿通路径的强直刺激诱导了突触传递的长时程增强，在所有组中都是可比的，与处理无关。因此，在依赖海马的学习任务中测试的选择准确性不受影响。然而，在接受 0.5 mmol/kg MnCl(2)的组中，同一任务的反应潜伏期大大增加。实验结束时对海马的免疫组织学检查未显示神经元毒性或神经胶质反应的迹象。尽管我们表明 0.1 mmol/kg MnCl(2 的 MEMRI 可以安全地应用于认知网络的研究，但强烈建议对每个特定的研究和 Mn(2+)给药方案进行毒性的详细评估。
