Process models of associative learning and related plasticity in primary sensory cortex.

巴甫洛夫反射条件反射的核心是联想学习，它将中性条件刺激(CS)的出现与生物相关的非条件刺激(US)联系起来，从而导致反射性无条件反应(UR)。由此形成的记忆可以被描述为“时空偶然性的存储”，通常被归类为内隐(程序性)记忆。除了这种核心联系之外，反射条件作用还涉及其他非常不同的行为机制。认知过程对形成外显(陈述性)记忆有重要作用，它确保受试者“理解游戏规则”。背景信息也被存储起来，最后但并非最不重要的是，情绪过程是激励动力的因素。重要的是，这些流程可能会彼此交互，也可能与核心关联交互。我们将这种不同的行为机制及其相互作用称为任务的过程模型。我们之前关于小鼠BCX(桶皮质；初级体感区域的胡须相关部分)在联想学习中的作用的工作表明，触觉轨迹眨眼条件反射(TEBC)形成了强大的学习相关网络和反应可塑性。在时间域上，TEBC在CS呈现期间，以及有趣的是，在无刺激跟踪期间，诱发了学习相关反应(LRA)。特定于时间的因果干扰显示，第一个对条件反应(CR)的产生是有益的，而第二个不是。因此，所发现的LRA可以部分地反映过程模型的“非核心”方面。该项目将研究BCX可塑性与认知加工和外显记忆形成有关的假设。我们将首先利用行为分析，找出小鼠在眨眼条件反射(EBC)过程中是否参与了外显和内隐形式的学习。EBC的延迟和踪迹变体的混合灭绝学习将被用来揭示这两个学习系统的相互作用，正如以前在人类中所做的那样。在下一步使用双光子显微镜，我们将测试观察到的BCX脊柱可塑性是否稳定，以应对任务过程模型的系统变化。为此，我们将训练小鼠，第二，延迟和跟踪EBC(D-T)的版本，以及第三，两个胡须的沉默联想(SIA)。D-T实验将使我们了解BCX的可塑性是否是外显学习和内隐学习交互作用的结果。SIA的实验将提供情绪过程在多大程度上推动可塑性的信息。在最后一个实验中，我们将阐明BCX可塑性在EBC学习中的因果作用是否由记忆巩固过程中神经元变化的时空特征决定。

The core of Pavlovian reflex conditioning is associative learning, linking the occurrence of a neutral conditioned stimulus (CS) to a biologically relevant unconditioned stimulus (US), which in turn leads to a reflexive unconditioned response (UR). The memory thus formed can be described as ‘storage of a spatio-temporal contingency’, and is often classified as implicit (procedural) memory. Beyond this core association, reflex conditioning in addition engages other, vastly different behavioral mechanisms. There is a critical contribution of cognitive processes, forming explicit (declarative) memory, which assure that the subject ‘understands the rule of the game’. Contextual information is stored as well, and last but not least, emotional processes factor in as motivational drive. Importantly, these processes potentially interact with each other and the core association. We call this diverse body of behavioral mechanisms and their interactions the task’s ‘process model’.Our previous work on the role of mouse BCx (barrel cortex; the whisker-related part of the primary somatosensory area) in association learning, demonstrated strong learning-related network and response plasticity formed by tactile trace eyeblink conditioning (TEBC). In the time domain, TEBC evoked learning related responses (LRA) during CS presentation, and interestingly, during the stimulus-free Trace period. Time-specific causal interference revealed that the first is instrumental for conditioned response (CR) generation, the core association, while the second is not. Thus, the found LRA may partially reflect ‘non-core’ aspects of the process model. The proposed project will investigate the hypothesis that BCx plasticity is related to cognitive processing and the formation of explicit memory.Using behavioral analysis we will firstly aim to find out whether mice engage explicit as well as implicit forms of learning during eyeblink conditioning (EBC). Mixed extinction learning of delay and trace variants of EBC will be employed to reveal the interaction of the two learning systems, as has been worked out previously in humans. In a next step using 2-photon microscopy, we will test whether the observed BCx spine plasticity is stable against systematic variation of the task’s process model. To this end, we will, secondly, train mice to delay and trace versions of EBC (D-T), as well as, thirdly, to silent associations (SiA) of two whiskers. The D-T experiments will give us insight whether BCx plasticity is due to interactions of explicit and implicit learning. The SiA experiments will provide information in how far emotional processes drive plasticity. In a last experiment, we will clarify whether the causal role of BCx plasticity on EBC learning is determined by spatio-temporal characteristics of neuronal changes during memory consolidation.