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

联想学习的特征是受试者的行为随着世界的相关变化而发生明智的变化。如果发出环境变化信号的感觉刺激在时间上与要适应的行为分开，两者的联系需要大脑的助记过程。在已建立的陈述性学习模型系统--示踪眨眼条件反射中，持续的mPFC神经元活动弥合了CS和CR之间的时间差距。初级感觉皮层对痕迹条件作用也很关键，但它们在弥合差距方面的确切机制作用仍然难以捉摸。在这里，我们建议研究小鼠的痕迹眨眼条件反射，利用可获得的痕迹眨眼条件反射范例的触觉变体，以及研究非常充分的初级体感区域BCX。我们的目标是阐明BCX是否以及如何代表助记信号，以及这是如何通过突触连接的重新安排来支持的。我们的起点是其他人以前的工作，这些工作表明BCX功能对于这一任务是必不可少的，我们使用2pi的初步工作表明，在跟踪条件作用过程中，L5锥体顶端树突上的树突刺被消除。在第一组实验中，将在BCX和mPFC中使用多点电生理学来搜索助记信号。在CS、TRACE和CR期间，将监测这两个结构中的协同活动。第二组实验将集中在使用基于病毒的追踪技术和2pi相结合的情况下，L1中突触前兴奋性轴突的数量是否与突触后棘相一致地改变。最后，在学习期间使用顶端树突的2pi钙成像，我们将阐明树突状簇状钙瞬变是否预测(以及可能导致)脊柱消除。

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.