Neurobiology of Sensory Preconditioning

感觉预处理的神经生物学

• 批准号: 10657204
• 负责人: Isaac Cervantes Sandoval
• 金额: $ 32.83万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657204
• 关键词: Animals; Association Learning; Behavior Control; Behavioral; Biological; Brain; Brain Diseases; Calcium; Categories; Cells; Complex; Conditioned Reflex; Cues; Data; Desire for food; Development; Dopamine; Dopamine Receptor; Drosophila genus; Environment; Feedback; Functional Imaging; Goals; Habits; Human; Imaging Techniques; Knowledge; Learning; Link; Memory; Memory Disorders; Memory impairment; Modeling; Molecular; Mushroom Bodies; Nature; Nervous System; Neurobiology; Neurons; Odors; Output; Phase; Policies; Predictive Value; Process; Research; Resolution; Role; Sensory; Shock; Signal Transduction; Stimulus; Structure; Synapses; Synaptic plasticity; System; Testing; Training; base; conditioned fear; conditioning; connectome; dopaminergic neuron; experience; experimental study; falls; fly; genetic manipulation; insight; knowledge base; memory encoding; nervous system disorder; novel; optogenetics; phase 3 testing; preconditioning; rational design; response; stimulus interval; theories; therapy design

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.

总结 学习和记忆存储是一个复杂的过程，已被证明具有挑战性。尽管取得了重大 在理解经典条件反射方面的进展，很可能在自然界中，强化的指导价值 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发生的。 价值来自环境的先前关联结构，而不仅仅是条件的连续性 无条件的这是相关的，因为看似中性的刺激之间的关联扩展了 创造有意义的关联和概括的可能性，并增加预测能力 每时每刻的体验。高阶条件反射福尔斯就属于这一类学习。这项建议 目的是了解嗅觉感觉预适应的生物学基础，这是一种高阶 条件反射具体来说，我们将使用行为和功能成像技术结合神经元成像技术， 和遗传操作，包括光遗传学，以定义感觉的基本规则和动力学， 预处理我们还将测试多巴胺调节在这种学习形式中的作用。最后，我们将测试 假设嗅觉表征在感觉预适应过程中发生改变， 表征是在无价值刺激之间形成关联的基础。长期目标是 一个建议是获得我们的大脑如何实现感官的生物学基础上的知识， 预处理 这一建议是非常有意义的，因为我们对高阶生物学基础的认识存在很大差距 条件反射此外，了解大脑疾病中记忆是如何编码和中断的， 这是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 是基于经典条件反射研究的然而，我们认为高阶条件作用是 比巴甫洛夫的联想在真实的自然主义情境中更相关。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导。 条件反射该项目将支持我们的长期目标，即理解记忆到单细胞， 亚细胞水平，为合理开发新疗法提供必要的知识基础 治疗记忆障碍