Analysis of the performance-enhancing effects of hippocampal lesions in rat serial reaction time task

顺序学习是知识获取的一种基本形式，即内隐或程序性学习，在人类和灵长类动物身上使用连续反应时间任务进行测试。在帕金森患者中，通过使用脑成像技术，可以证明额纹状体和多巴胺能过程在顺序行为中起着核心作用。我们开发了一个具有高表面效度的连续反应时间任务的大鼠版本，以研究包括操纵方法在内的神经机制，我们的翻译研究验证了测试表明，多巴胺损伤可以损害序列行为，特别是在学习过程中。最近，我们研究了海马体，它被认为在外显和空间学习和记忆中发挥作用。令人惊讶的是，我们反复发现，海马区的损伤大大提高了我们的任务中的表现，这支持了一种假设，即基底节和海马体同时提供给额叶皮质部位的信息在顺序学习过程中可以相互竞争，而海马区信息在顺序学习过程中可能不起关键作用。在这里，我们想要解决一些关于这种损害效应的尚未解决的问题：a)成绩提高效应是顺序学习所特有的，还是它改善了我们任务中所需的工具性学习；b)为额叶皮质部位提供重要输入的中间海马区的损害是否足以产生这种效应？c)这些效应是任务获得所特有的吗？它们是否也可以由可逆性的药物阻断海马体诱导？

Sequential learning is a basic form of knowledge acquisition, namely implicit or procedural learning, which is tested in humans and primates using serial reaction time tasks. In Parkinson patients and by use of brain imaging techniques, it could be shown that fronto-striatal and dopaminergic processed play a central role in sequential behavior. We have developped a rat version with high face validity of the serial reaction time task to study neural mechanisms including manipulative approaches, and our translational studies to validate the test showed that dopamine lesions can impair sequential behavior, especially during learning. More recently, we studied the hippocampus, which is thought to play a role for explicit and spatial learning and memory. Surprisingly, we repeatedly found that lesions of the hippocampus substantially enhanced performance in our task, which supports the hypothesis that simultaneous information provided by basal ganglia and hippocampus to frontal cortical sites can compete with each other during sequential learning and that hippocampal information may not play a crucial role during sequential learning. Here, we want to address some yet unresolved questions regarding this lesion effect: a) Is the performance-enhancing effect specific for sequential learning or does it improve instrumental learning which is required in our task, b) are lesions of the intermediate hippocampus, which provided important inputs to frontal cortical sites, sufficient for the effect?, and c) are the effects specific for task acquisition and can they also be induced by reversible pharmacological blockade of the hippocampus?