Lobaugh N J, Norton D, Novak K, Amsel A
Department of Psychology, University of Texas at Austin 78712, USA.
Neurobiol Learn Mem. 1995 Jan;63(1):94-106. doi: 10.1006/nlme.1995.1009.
Three experiments are presented in which the neural and behavioral consequences of multiple ibotenic acid (IBO) injections into the hippocampus were examined in Sprague-Dawley rat pups. Rat pups were 11 or 15 days of age at the time of surgery (SURG11, SURG15), the dose of IBO was either 1 microgram in 1 microliter, 2.5 micrograms in 0.5 microliters, or 5 micrograms in 1 microliter for each of four injections, and pups were allowed to survive for 3 or 7 days after the lesion was made. The Fink-Heimer silver stain was used in Experiment 1 to examine the extent of neural damage following unilateral lesions and showed that the degeneration was primarily located in the hippocampus. The magnitude of the damage was greatest in younger pups and in those which received the higher of the two concentrations (injection volume was not a factor). Degenerating fibers were seen in the columns of the fornix as well as precommissural fornix fibers, but only in SURG15 animals when damage extended into the dorsal subiculum. Mortality rates following multiple IBO injections were very high in infant rats, in some cases as high as 60%. Experiments 2 and 3 examined the effects of bilateral lesions on neuroanatomy and behavior. Bilateral lesions were somewhat smaller than unilateral lesions, and as for unilateral lesions, degeneration in pre- and postcommissural fornix was seen only in SURG15 animals. The behavioral task used in Experiments 2 and 3 was patterned single alteration, a memory-based appetitive learning discrimination. Earlier work has shown that damage to the infant hippocampus results in moderate deficits in this task at 30-s intervals and more substantial deficits at 60-s intertrial intervals. This was not the case in the present studies: regardless of age at surgery or time postlesion, all infant rats tested learned this discrimination at the two intertrial intervals. As has been recently reported for adult rats, excitotoxic lesions of the hippocampus in infant rats do not produce the same patterns of behavioral deficits as electrolytic lesions.
本文介绍了三项实验，研究了向Sprague-Dawley幼鼠海马体多次注射鹅膏蕈氨酸（IBO）后的神经和行为后果。手术时（SURG11、SURG15）幼鼠的年龄为11或15天，每次四次注射中，IBO的剂量分别为1微升含1微克、0.5微升含2.5微克或1微升含5微克，造模后让幼鼠存活3或7天。实验1使用Fink-Heimer银染法检查单侧损伤后的神经损伤程度，结果显示变性主要位于海马体。损伤程度在较年幼的幼鼠以及接受两种浓度中较高浓度（注射体积不是因素）的幼鼠中最大。在穹窿柱以及连合前穹窿纤维中可见变性纤维，但仅在损伤扩展至背侧下托的SURG15动物中出现。多次注射IBO后，幼鼠的死亡率非常高，在某些情况下高达60%。实验2和3研究了双侧损伤对神经解剖和行为的影响。双侧损伤比单侧损伤稍小，与单侧损伤一样，仅在SURG15动物中观察到连合前和连合后穹窿的变性。实验2和3中使用的行为任务是模式化单次改变，这是一种基于记忆的食欲性学习辨别。早期研究表明，幼鼠海马体损伤在30秒间隔时会导致该任务出现中度缺陷，在60秒试验间隔时会导致更严重的缺陷。但在本研究中并非如此：无论手术时的年龄或损伤后的时间如何，所有接受测试的幼鼠在两个试验间隔时都学会了这种辨别。正如最近针对成年大鼠所报道的那样，幼鼠海马体的兴奋性毒性损伤不会产生与电解损伤相同的行为缺陷模式。
