Revealing neocortical mechanisms for declarative learning: Functional role and cellular mechanisms of primary sensory cortex plasticity for trace eyeblink conditioning in mice.

点击翻译按钮获取中文摘要

Associative learning is characterized by sensible alterations in the behavior of a subject in response to relevant changes in the world. In case the sensory stimulus signaling the changed environment is temporally separate from the to-be-adapted behavior, the association of the two requires mnemonic brain processes. In trace eyeblink conditioning, an established model system for declarative learning, the temporal gap between the CS and the CR is bridged by sustained mPFC neuronal activity. Primary sensory cortices are critical for trace conditioning too, but their exact mechanistic role in bridging the gap is still elusive. Here we propose to study mouse trace eyeblink conditioning, taking advantage of the availability of a tactile variant of the trace eyeblink conditioning paradigm, and the very well-studied primary somatosensory area BCx. We aim at elucidating whether and how BCx represents mnemonic signals and how this is underpinned by re-arrangement of synaptic connections. Our starting point is previous work by others that showed that BCx function is indispensable for this task, and our preliminary work using 2PI that showed that dendritic spines on apical dendrites of L5 pyramids in L1 are eliminated during trace conditioning. In a first set of experiments, mnemonic signals will be searched employing multi-site electrophysiology in BCx and mPFC. Concerted activity in the two structures will be monitored during CS, trace and CR periods. A second set of experiments will focus on the question whether the number of presynaptic excitatory axonal boutons in L1 is changed in concert with the postsynaptic spines using virus-based tracing techniques in combination with 2PI. Finally, using 2PI calcium imaging of apical dendrites during learning we will elucidate whether dendritic tuft calcium transients predict (and possibly cause) spine elimination.