恒河猴,懒猴和树Qu的短时空间记忆功能与前额叶背侧部进化水平的相关性

本文研究探讨了进化地位不同的三种动物的短时空间记忆功能及其与前额叶背侧部进化水平的相关性。结果表明,在延缓反应作业中,经1000次训练后,7只恒河猴对空间位置的记忆时间平均为7.7±3.2 min,懒猴为3.8±0.44 min,而树qu即使在延缓时间几乎为零秒的延缓反应中,其正确反应率也未达到90%标准。一种延缓时间仅测试一个单元,即不经训练的实验表明,恒河猴在延缓期为“0”-5 min的各测试单元中,正确反应率稳定在80%以上;懒猴在延缓时间为“0”-4 min的各测试单元中,平均正确反应率与恒河猴无明显差异,而当延缓时间增加到5 min时,在延缓反应作业中取得的成绩显著下降;树qu在延缓时间为1-5 min的作业中取得的正确反应率在70%以下。3种动物在视觉辨别学习作业中却无明显差异。形态学研究表明,灵长类大脑前额叶的面积和结构的复杂性在进化过程中逐渐增大,如恒河猴大脑前额叶的表面积占大脑半球表面积的11.5%（Brodmann,1929）,其内颗粒层发达,背侧部明显凸起,主沟区发达;懒猴的前额叶表面积占其大脑半球表面积的8.3%,背侧部凸起不显著,主沟未形成,额极内颗粒层分化明显,背侧部的内颗粒层较内侧部的发达程度差（Sanides,1967）;树qu的前额叶表面积占7.5%,额极的内颗粒层分化不明显,为非颗粒化区,此区之后为颗粒区和运动前区,颗粒区背侧部的发育程度明显较内侧部差。恒河猴前额叶损伤研究结果表明,短时空间记忆功能依赖前额叶背侧部的完整性。本研究提示,短时空间记忆功能的发达程度与大脑前额叶背侧部的进化程度有相关性。     

树鼩模型:抑郁症的社会竞争失败与学习和记忆的被捕获条件反射

最近基因组研究表明树鼩属于灵长类或是与灵长类亲缘关系最密切的姐妹种.因此,树鼩可能是应用于建立人类疾病动物模型的最佳动物之一.该文报道一种抑郁症的社会竞争失败病因学树鼩(Tupaia belangerichinensis)模型.一对雄性树鼩被饲养在一个双笼中,用网格把双笼隔开,网格上有一小门.适应1周后,把小门打开,这一对树鼩产生短暂的争斗,每天一次,连续21天.其中争斗失败者被称为服从者.这个过程可导致每天1 h的直接社交冲突和23 h的间接相互影响(比如通过气味、视觉等).与正常对照相比,失败者在第三周也就是社交冲突的最后一周显示了体重、自主活动、躲避行为、尿液皮质醇水平等的变化,并且这种改变可持续至少2周以上.此外,还报道全新的记忆模型,一种被捕获条件反射树鼩模型.在一个封闭的小房间中放置捕获笼,其中挂有一片苹果,小房间中有一只自由活动的树鼩.训练的前4次树鼩进入捕获笼吃苹果并不触发捕获笼关闭,但在第5次时触发捕获笼关闭,并持续一小时才释放树鼩.第1-5次树鼩进入捕获笼的延迟时时间作为适心性指标,其中第5次才是作为被捕获的一次学习训练.24 h后,测试树鼩进入捕获笼的延迟时间作为被捕获记忆能力指标.树鼩经过第5次被捕获训练,能形成很好的被捕获记忆,因为24 h后的延迟时间极人地增加.在训练前腹腔注射已知能阻断记忆形成的NMDA受体拮抗剂MK-801(0.2 mg/kg,腹腔注射),对适应指标没有显著影响,但足极大地缩短了24 h后测试的延迟时间,即阻断了被捕获记忆.这些结果表明了一种抑郁症的慢性社会竞争失败与学习和记忆的一次被捕获条件反射树鼩模型.这两种树趵模型对抑郁症与学习和记忆的机理研究、抗抑郁症新药的临床前药效学评价具有潜在的重要意义.

Abstract：

Recent genome studies indicate that tree shrew is in the order or a closest sister of primates, and thus may be one of the best animals to model human diseases. In this paper, we report on a social defeat model of depression in tree shrew (Tupaia belangeri chinensis). Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages. After one week adaptation, the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict (fighting) and 23 h indirect influence (e.g. smell, visual cues) per day for 21 days. The defeated tree shrew was considered the subordinate. Compared with naive animals, subordinate tree shrews at the final week of social conflict session showed alterations in body weight, locomotion, avoidance behavior and urinary cortisol levels.Remarkably, these alterations persisted for over two weeks. We also report on a novel captive conditioning model of learning and memory in tree shrew. An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew. For the first four trials, the tree shrew was not trapped when it entered the cage and ate the bait apple, but it was trapped and kept in the cage for 1 h on the fifth trial. Latency was defined as the time between release of the tree shrew and when it entered the captive cage. Latencies during the five trials indicated adaptation. A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory. Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials. The N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (0.2 mg/kg, i.p.), known to prevent the formation of memory, did not affect latencies in the adaptation trails, but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial. These results demonstrate a chronic social defeat model of depression and a novel one-trial captive conditioning model for learning and memory in tree shrews, which are important for mechanism studies of depression, learning,memory, and preclinical evaluation for new antidepressants.