Neurobiology of Sensory Preconditioning

摘要 学习和记忆存储是一个复杂的过程，事实证明，这一过程具有挑战性。尽管意义重大 在理解经典条件反射的进展中，很可能在本质上具有补益的指导价值 经验是后天获得的，而不是天生的。换句话说，我们的许多学习经历都是通过推理来实现的 来自环境的先前关联结构的值，而不是仅仅通过条件的邻接性 而且是无条件的。这是相关的，因为看似中性的刺激之间的关联扩大了 创造有意义的联想和概括的可能性范围，并增加预测能力 每时每刻的体验。高阶条件反射就属于这一类学习。这项建议 旨在了解嗅觉预适应的生物学基础，嗅觉预适应是一种高阶 条件反射。具体地说，我们将使用行为和功能成像技术，结合神经元 以及基因操作，包括光遗传学，以定义感官的基本规则和动力学 预适应。我们还将测试多巴胺调制在这种学习形式中的作用。最后，我们将测试 嗅觉表征在感觉预适应过程中发生改变的假说 表征是在毫无价值的刺激之间形成联系的基础。这样做的长期目标是 建议是在我们的大脑如何实现感觉的生物学基础上获得知识 预适应。 这一建议意义重大，因为我们对高阶生物基础的认识存在很大差距。 条件反射。此外，了解记忆是如何在大脑紊乱中编码和破坏的是一种 合理设计记忆障碍治疗方法的先决条件。我们对记忆形成的理解 在很大程度上基于经典的条件作用研究。然而，我们认为高阶条件反射是 在真实的自然主义情况下，比巴甫洛夫式的联想更相关。本研究的结果 将为未来研究高阶记忆形成的神经生物学提供指南 条件反射。该项目将支持我们理解记忆的长期目标，深入到单细胞和 亚细胞水平，有助于合理开发新疗法所需的知识基础 对于记忆力受损。

Summary Learning and memory storage is a complex process that has proven challenging to tackle. Despite significant progress in understanding classical conditioning, it is likely that in nature, the instructive value of reinforcing experiences is acquired rather than innate. In other words, many of our learning experiences occur by inferring value from a previously associative structure of the environment and not by the mere contiguity of conditioned and unconditioned. This is relevant because the association between seemingly neutral stimuli expands the gamut of possibilities to create meaningful associations and generalizations and increases the predictive power of moment-by-moment experiences. High-order conditioning falls within this category of learning. This proposal aims to understand the biological basis of olfactory sensory preconditioning, a form of high-order conditioning. Specifically, we will use behavioral and functional imaging techniques combined with neuronal and genetic manipulations, including optogenetics, to define the basic rules and dynamics of sensory preconditioning. We will also test the dopamine modulation’s role in this form of learning. Finally, we will test the hypothesis that olfactory representations are altered during sensory preconditioning and that this altered representation is fundamental for forming associations between valueless stimuli. The long-term goal of this proposal is to gain knowledge on the biological basis of how our brain achieves sensory preconditioning. This proposal is highly significant because there is a big gap in our knowledge of biological basis of high-order conditioning. In addition, understanding how memories are encoded and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Our understanding of memory formation is based heavily on classical conditioning research. Nevertheless, we argue that high-order conditioning is more relevant than Pavlovian association in real naturalistic situations. The results of the present studies will provide guideposts for future research into the neurobiology of memory formation during high-order conditioning. The project will support our long-term goal of understanding memory down to the single-cell and subcellular levels, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.