Marighetto A, Micheau J, Jaffard R
Laboratoire de Neurosciences comportementales et Cognitives, CNRS URA 339, Université de Bordeaux I, Talence, France.
Behav Brain Res. 1993 Sep 30;56(2):133-44. doi: 10.1016/0166-4328(93)90031-k.
Alterations in hippocampal cholinergic activity associated with different types and/or stages of learning were explored using measures of sodium-dependent high-affinity choline uptake (SDHACU) in the hippocampus of C57BL/6 mice. Animals were divided into 'active' subjects submitted to memory testing before being killed and 'quite' controls. 'Active' subjects were trained in a radial-arm maze on either a discrimination task (mixed Working Memory (WM)-Reference Memory (RM) task) or a Delayed-Non-Matching-To-Place task (more selective WM-task). In the discrimination task mice were sacrificed after either the 1st, 2nd, 3rd or 9th daily session of training and at intervals of either 30 s, 15 min, 24 h or 9 days post-test. In the DNMTP-task all subjects of the 'active' groups were sacrificed after 12 days of training at either 30 s or 24 h post-test. Results showed that: (1) Both types of training induced an immediate (30 s post-test) increase of hippocampal SDHACU as compared to 'quite' control condition. (2) In the discrimination task, this immediate increase in SDHACU was followed by a decrease leading to a long-lasting (24 h and 9 days) inhibition of this cholinergic marker. This secondary decrease in SDHACU occurred earlier (15 min post-test) at the end (9th session) than at the beginning (1st-3rd sessions) of training. Thus, as training progressed there was a shortening of the testing-induced cholinergic activation. (3) By contrast, in the DNMTP-task, SDHACU was still increased at the interval of 24 h following the last session of DNMTP-training. (4) The amplitudes of both the immediate (30 s) increase and subsequent secondary (15 min) decrease in SDHACU after the last (9th) session of discrimination training were significantly related to the rate of acquisition and behavioural profile for individual animals. Subjects that had displayed better response accuracy across the 9 days of training exhibited the highest SDHACU at 30 s post-test and the lowest at 15 min post-test. These results are discussed in the context both of previous findings on the effects of training on cholinergic activity, and of contemporary models of hippocampal function. It is suggested that (1) an increase in hippocampal cholinergic transmission during testing would facilitate the acquisition of a 'relational' kind of informations (spatial WM and RM); (2) the post-training consolidation (spatial RM) of information would be facilitated by a decrease and long-lasting inhibition of hippocampal cholinergic activity.
利用对C57BL/6小鼠海马中钠依赖性高亲和力胆碱摄取（SDHACU）的测量，探究了与不同类型和/或学习阶段相关的海马胆碱能活性变化。动物被分为在处死前接受记忆测试的“活跃”组和“安静”对照组。“活跃”组动物在放射状臂迷宫中接受辨别任务（混合工作记忆（WM）-参考记忆（RM）任务）或延迟非匹配位置任务（更具选择性的WM任务）训练。在辨别任务中，小鼠在训练的第1、2、3或9天每日训练课程后，以及测试后30秒、15分钟、24小时或9天的间隔时间处死。在DNMTP任务中，“活跃”组的所有动物在训练12天后，于测试后30秒或24小时处死。结果表明：（1）与“安静”对照组相比，两种类型的训练均导致海马SDHACU在测试后立即（30秒）增加。（2）在辨别任务中，SDHACU的这种立即增加之后是下降，导致该胆碱能标志物的长期（24小时和9天）抑制。SDHACU的这种继发性下降在训练结束时（第9次训练课程）比开始时（第1 - 3次训练课程）更早（测试后15分钟）出现。因此，随着训练的进行，测试诱导的胆碱能激活时间缩短。（3）相比之下，在DNMTP任务中，在DNMTP训练的最后一次课程后24小时的间隔时间内，SDHACU仍然增加。（4）在辨别训练的最后一次（第9次）课程后，SDHACU立即（30秒）增加和随后继发性（15分钟）下降的幅度与个体动物的习得率和行为特征显著相关。在9天训练中表现出更好反应准确性的动物在测试后30秒时SDHACU最高，在测试后15分钟时最低。这些结果在先前关于训练对胆碱能活性影响的研究结果以及当代海马功能模型的背景下进行了讨论。研究表明：（1）测试期间海马胆碱能传递的增加将促进“关系性”信息（空间WM和RM）的习得；（2）海马胆碱能活性的降低和长期抑制将促进训练后信息的巩固（空间RM）。
