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

巴甫洛夫反射条件作用的核心是联想学习，将中性条件刺激（CS）的发生与生物相关的非条件刺激（US）联系起来，后者反过来导致反射性非条件反应（UR）。这样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）记忆。除了这一核心联系之外，反射条件反射还涉及其他截然不同的行为机制。认知过程的一个重要贡献是，形成显性（陈述性）记忆，确保受试者“理解游戏规则”。情境信息也被存储，最后但并非最不重要的是，情绪过程作为动机驱动因素。重要的是，这些过程可能相互作用，并与核心关联。我们把这种多样的行为机制及其相互作用称为任务的“过程模型”。我们之前对小鼠BCx（桶状皮质，初级体感区域的须相关部分）在联想学习中的作用的研究表明，触觉痕迹眨眼条件反射（TEBC）形成了强大的学习相关网络和反应可塑性。在时域上，TEBC在CS呈现期间诱发了学习相关反应（LRA），有趣的是，在无刺激的Trace期间也诱发了学习相关反应。时间特异性的因果干扰表明，前者有助于条件反应（CR）的产生，而后者则不是。因此，发现的LRA可能部分反映流程模型的“非核心”方面。本项目将研究脑皮层可塑性与认知加工和外显记忆形成有关的假设。通过行为分析，我们将首先找出小鼠在眨眼条件反射（EBC）过程中是否参与外显和内隐形式的学习。延迟和EBC的痕量变体的混合灭绝学习将被用来揭示两个学习系统的相互作用，就像以前在人类中研究出来的那样。在下一步使用双光子显微镜，我们将测试观察到的BCx脊柱可塑性是否对任务过程模型的系统变化是稳定的。为此，我们将，其次，训练小鼠延迟和追踪EBC （D-T）版本，以及，第三，两个胡须的沉默关联（SiA）。D-T实验将让我们了解BCx可塑性是否由于外显和内隐学习的相互作用。SiA的实验将提供有关情绪过程在多大程度上推动可塑性的信息。在最后一项实验中，我们将阐明BCx可塑性对EBC学习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.