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

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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.