Department of Psychology, Northwestern University, 2029 Sheridan Rd., Evanston, IL 60208, USA.
Hippocampus. 2012 Jun;22(6):1242-55. doi: 10.1002/hipo.20998. Epub 2011 Dec 19.
The hippocampal mossy fibers (MFs) are capable of behaviorally selective, use-dependent structural remodeling. Indeed, we previously observed a new layer of Timm's staining induced in the stratum oriens (SO) in CA3 after spatial but not cued water maze learning (Rekart et al., (2007) Learn Mem 14:416-421). This led to the prediction that there is a learning-specific induction of presynaptic terminal plasticity of MF axons. This study confirms this prediction demonstrating, at the confocal level of analysis, terminal-specific, and behavior-selective presynaptic structural plasticity linked to long-term memory. Male adult Wistar rats were trained for 5 days to locate a hidden or visible platform in a water maze and a retention test was performed 7 days later. MF terminal subtypes, specifically identified by an antibody to zinc transporter 3 (ZnT3), were counted from confocal z-stacks in the stratum lucidum (SL) and the SO. In hidden platform trained rats, there was a significant increase in the number of large MF terminals (LMTs, 2.5-10 μm diameter, >2 μm(2) area) compared to controls both in the proximal SL (P < 0.05) and in the SO (P < 0.01). Surprisingly, there was no detectable increase in small MF terminals (SMTs, 0.5-2 μm diameter, <2 μm(2) area) in either SL or SO as a consequence of training. This distinction of the two MF terminal types is functionally important as LMTs synapse on CA3 pyramidal neurons, while SMTs are known to target inhibitory interneurons. The present findings highlight the pivotal role in memory of presynaptic structural plasticity. Because the "sprouting" observed is specific to the LMT, with no detectable change in the number of the SMT, learning may enhance net excitatory input to CA3 pyramidal neurons. Given the sparse coding of the MF-CA3 connection, and the role that granule cells play in pattern separation, the remodeling observed here may be expected to have a major impact on the long-term integration of spatial context into memory.
海马苔藓纤维（MFs）具有行为选择性、使用依赖性的结构重塑能力。事实上，我们之前观察到，在空间而非提示水迷宫学习后，CA3 的放射状层（SO）中诱导了一层新的 Timm 染色（Rekart 等人，（2007）学习记忆 14:416-421）。这导致了这样的预测，即 MF 轴突的突触前末端可塑性有特定的学习诱导。这项研究证实了这一预测，在共聚焦分析水平上，证明了与长期记忆相关的特定于末端和行为选择性的突触前结构可塑性。雄性成年 Wistar 大鼠接受了 5 天的训练，以在水迷宫中找到隐藏或可见的平台，然后在 7 天后进行保留测试。通过锌转运蛋白 3（ZnT3）抗体特异性鉴定 MF 末端亚型，在透明层（SL）和 SO 的共聚焦 z 堆栈中进行计数。在隐藏平台训练的大鼠中，与对照组相比，近端 SL（P < 0.05）和 SO（P < 0.01）中，大 MF 末端（LMTs，2.5-10 μm 直径，>2 μm(2) 面积）的数量显著增加。令人惊讶的是，无论是在 SL 还是 SO，训练后都没有检测到小 MF 末端（SMTs，0.5-2 μm 直径，<2 μm(2) 面积）的增加。这两种 MF 末端类型的区分在功能上很重要，因为 LMTs 与 CA3 锥体神经元形成突触，而 SMTs 已知靶向抑制性中间神经元。目前的发现强调了突触前结构可塑性在记忆中的关键作用。由于观察到的“发芽”是特定于 LMT 的，并且 SMT 的数量没有检测到变化，因此学习可能会增强 CA3 锥体神经元的净兴奋性输入。鉴于 MF-CA3 连接的稀疏编码以及颗粒细胞在模式分离中的作用，这里观察到的重塑可能会对长期将空间上下文整合到记忆中产生重大影响。
