Department of Psychology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
Hippocampus. 2011 May;21(5):532-40. doi: 10.1002/hipo.20786.
Learning a spatial location induces remodeling of the mossy fiber terminal field (MFTF) in the CA3 subfield of the dorsal hippocampus (Ramirez-Amaya et al. (2001) J Neurosci 21:7340-7348; Holahan et al. (2006) Hippocampus 16:560-570; Rekart et al. (2007a) Learn Mem 14:416-421). These fibers appear to grow from the stratum lucidum into distal stratum oriens. Is this axonal growth dependent on “repeated and persistent” neural activity in the CA3 region during training? To address this issue, we targeted local inactivation of the MFTF region in a post-training, consolidation paradigm. Male Wistar rats, bilaterally implanted with chronic indwelling cannulae aimed at the MFTF CA3 region, were trained on a hidden platform water maze task (10 trials per day for 5 days). Immediately after the 10th trial on each training day, rats were injected with lidocaine (4% w/v; 171 mM; n=7) or phosphate-buffered saline (PBS; n=7). Behavioral measures of latency, path length, and thigmotaxis were recorded, as was directional heading. A retention test (probe trial) was given 7 days after the last training day, and brains were subsequently processed for MFTF distribution (Timm's stain) and cannula location. Lidocaine treatment was found to block the learning-associated structural remodeling of the MFTF that was reported previously and observed in the PBS-injected controls. During training, the lidocaine group showed elevated latencies and a misdirected heading to locate the platform on the first trial of each training day. On the 7-day retention probe trial, the lidocaine-injected group showed poor retention indicated by the absence of a search bias in the area where the platform had been located during training. These data suggest that the reduction of neuronal activity in the CA3 region impairs long-term storage of spatial information. As this was associated with reduced MFTF structural remodeling, it provides initial anatomical and behavioral evidence for an activity-dependent, presynaptic growth model of memory.
学习空间位置会诱导背侧海马 CA3 亚区苔藓纤维末梢场（MFTF）的重塑（Ramirez-Amaya 等人，2001 年，《神经科学杂志》21：7340-7348；Holahan 等人，2006 年，《海马体》16：560-570；Rekart 等人，2007a 年，《学习记忆》14：416-421）。这些纤维似乎从透明层延伸到远端的锥体细胞层。这种轴突生长是否依赖于训练期间 CA3 区“反复和持续”的神经活动？为了解决这个问题，我们在训练后的巩固范式中靶向 MFTF 区域的局部失活。雄性 Wistar 大鼠双侧植入慢性留置套管，针对 MFTF CA3 区域，在隐藏平台水迷宫任务中进行训练（每天 10 次，连续 5 天）。在每天第 10 次训练后，立即向大鼠注射利多卡因（4%w/v；171mM；n=7）或磷酸盐缓冲盐水（PBS；n=7）。记录潜伏期、路径长度和趋触性等行为测量结果，以及定向朝向。在最后一次训练后的第 7 天进行保留测试（探针测试），随后对大脑进行 MFTF 分布（Timm 染色）和套管位置处理。研究发现，利多卡因处理阻断了先前报道的和在 PBS 注射对照组中观察到的与学习相关的 MFTF 结构重塑。在训练过程中，利多卡因组在每天训练的第一试中表现出潜伏期延长和定向错误，以定位平台。在 7 天的保留探针测试中，利多卡因注射组表现出较差的保留，在训练期间平台所在区域没有搜索偏差。这些数据表明，CA3 区神经元活动的减少会损害空间信息的长期储存。由于这与 MFTF 结构重塑减少有关，因此它为记忆的活动依赖性、突触前生长模型提供了初步的解剖学和行为证据。
