Mechanisms in the Expression and Decay of Long-Term Habituation Memory

描述（由申请人提供）：学习产生行为，生理和基因表达的长期变化。虽然这一原理现在在动物界得到了很好的证明，但学习和记忆的基本方面仍然不清楚：1）支持长期记忆的生理和遗传变化如何整合到神经回路中。2)遗忘是否代表长期记忆过程的衰退或主动擦除过程，以及3）记忆获得和保持的个体差异如何产生。为了解决学习和记忆中的这些基本问题，我们提出了一组简单的实验，使用长期习惯性的Aussia尾巴引起的虹吸回缩反射（T-SWR）。将动物组暴露于长期习惯性训练（5个区块，每区块30个刺激施加于尾部的一侧，30 s ISI，区块之间90分钟）。这种训练会导致T-SWR行为的长期和单侧下降。为了确定LTH的生理相关性，将对经过训练的动物进行麻醉，并将其减少到虹吸+尾部准备，从而能够在持续行为期间从T-SWR回路进行生理记录。通过比较来自每只动物的训练侧和未训练侧的尾部诱发的神经活动，将有可能识别由LTH训练引起的长期神经可塑性的位点。在生理记录之后，来自T-SWR回路的每一层的训练侧和未训练侧的神经元将被物理隔离。为了确定LTH的分子相关性，将从收获的细胞中提取RNA，逆转录，并使用微阵列进行分析。通过对训练后1天和7天收获的动物重复该相同程序，将有可能确定记忆表达（1天）和衰退（7天）的生理和遗传相关性。此外，组内分析将使识别的生理和转录因子，预测相当大的变化明显的收购和衰减的长期习惯。最后，LTH相关确定与这种方法将实验操作，以确定他们的休闲作用的表达和衰减的LTH记忆。这个项目提供了一个易于处理的手段，以获得基本的洞察长期记忆的机制，在实验的背景下，提供了良好的机会，本科生参与。 公共卫生相关性：该项目将探索介导习惯化长期记忆的遗传和神经变化，习惯化是整个动物王国共享的一种简单形式的记忆。通过研究一个简单的模式生物（Aaprosia californica）的习惯化机制，将有可能获得对记忆存储和随后衰减过程的基本见解。研究结果可能不仅对记忆障碍的治疗有意义，而且对被认为依赖于习惯化的各种注意力过程也有意义。

DESCRIPTION (provided by applicant): Learning produces long-term changes in behavior, physiology, and gene expression. Although this principle is now well-documented across the animal kingdom, fundamental aspects of learning and memory remain unclear: 1) how physiological and genetic changes supporting long-term memory are integrated across a neural circuit. 2) if forgetting represents the decay of long-term memory processes or an active erasure process, and 3) how individual differences in memory acquisition and retention arise. To address these fundamental issues in learning and memory, we propose a simple set of experiments using long-term habituation of the Aplysia tail-elicited siphon-withdrawal reflex (T-SWR). Groups of animals will be exposed to long-term habituation training (5 blocks of 30 stimuli applied to one side of the tail, 30s ISI, 90 min between blocks). This training produces a long-lasting and unilateral decrease in T-SWR behavior. To determine the physiological correlates of LTH, trained animals will be anesthetized and reduced to a siphon+tail preparation, enabling physiological recordings from the T-SWR circuit during ongoing behavior. By comparing tail-evoked neural activity from the trained and untrained side of each animal, it will be possible to identify sites of long- term neural plasticity elicited by LTH training. After physiological recordings, neurons from trained and untrained sides of each layer of the T-SWR circuit will be physically isolated. To determine the molecular correlates of LTH, RNA from harvested cells will be extracted, reverse-transcribed, and profiled using microarrays. By repeating this same procedure with animals harvested 1 and 7 days after training, it will be possible to determine physiological and genetic correlates of a memory expression (1 day) and decay (7 days). In addition, within group analyses will enable identification of physiological and transcriptional factors that predict the considerable variability evident in the acquisition and decay of long-term habituation. Finally, LTH correlates identified with this approach will be experimentally manipulated to determine their casual role in the expression and decay of LTH memory. This project provides a tractable means to gain fundamental insight into the mechanisms of long-term memory in an experimental context that offers excellent opportunities for undergraduate involvement. PUBLIC HEALTH RELEVANCE: This project will explore the genetic and neural changes that mediate long-term memory for habituation, a simple form of memory that is shared across the entire animal kingdom. By studying the mechanisms of habituation in a simple model organism (Aplysia californica), it will be possible to gain fundamental insight into the processes by memories are stored and subsequently decay. Results may have implications not only for the treatment of memory disorders, but also for a variety of attentional processes thought to depend on habituation.