Role of different neural pathways during memory consolidation

描述（由申请人提供）：了解记忆巩固的神经生物学对于记忆相关疾病，如恐惧症和创伤后应激障碍（PTSD）至关重要。以前的研究调查巩固的神经回路主要集中在回路中的单个“节点”，而不是大脑区域之间的神经连接，尽管这些连接在介导不同方面或形式的记忆中可能很重要。这种关注在一定程度上是由于技术限制;然而，光遗传学的出现改变了我们在这方面的能力，使我们能够以时间和空间精度对神经通路进行光学控制。因此，目前的提议将利用光遗传学来控制大鼠在不同类型学习后立即连接大脑区域的特定通路的活动。具体来说，我们将重点关注杏仁核（BLA），它长期以来一直与恐惧症和创伤后应激障碍等疾病有关，并已被证明可以调节各种类型学习的记忆巩固。这种影响许多类型记忆巩固的能力被认为是通过对不同大脑区域的离散投射来介导的，包括参与记忆更具体方面的丘脑核（NA）。事实上，NA亚区，核心和壳，都是已知的BLA和以前的研究表明，他们可能有不同的角色在记忆处理相关的上下文和伤害性（如footshock）学习，如参与上下文恐惧条件反射（CFC）。因此，为了更好地理解在不同类型的学习巩固过程中不同的BLA投射到NA的作用，我们将使用光遗传学来获得对特定BLA的控制NA途径（壳与核心）在训练后巩固期。具体地，目前的提议将利用BLA的光遗传学刺激或抑制。NAshell与BLANAcore途径，以影响记忆巩固训练后的修改CFC的任务，其中伤害性或情绪刺激（电击脚）和上下文是分开的，使实验操作选择性地影响巩固学习一个组件，而不是其他。在目标1中，我们将光学刺激不同的BLANA途径，以了解其各自的作用，在巩固的背景与footshock学习。目标2将通过光学抑制BLA来提供这些途径的功能丧失的补充检查NA途径后立即培训每一种学习。在这两个目标中，在相关训练后立即对每个候选途径进行光遗传学刺激/抑制，以确定其在影响CFC学习的该组成部分的巩固中的作用。这些结果将是第一个表明，BLA输入到不同的结构选择性地调节巩固学习的不同方面，从而提高了我们的理解巩固上下文恐惧条件反射的神经连接的基础，并为未来的研究提供了一个重要的基础。

DESCRIPTION (provided by applicant): Understanding the neurobiology of memory consolidation is critical for memory-related disorders, such as phobias and posttraumatic stress disorder (PTSD). Previous research investigating the neural circuitry underlying consolidation has primarily focused on single "nodes" in the circuit rather than the neural connections between brain regions, despite the likely importance of these connections in mediating different aspects or forms of memory. This focus has, in part, been due to technical limitations; however the advent of optogenetics has altered our capabilities in this regard, enabling optical control over neural pathways with temporal and spatial precision. The current proposal, therefore, will take advantage of optogenetics to control activity in specific pathways connecting brain regions in rats immediately after different kinds of learning. Specifically, we will focus on the basolaterl amygdala (BLA) which has long been implicated in disorders such as phobias and PTSD and has been shown to modulate memory consolidation for a variety of types of learning. This ability to influence the consolidation for many types of memory is believed to be mediated through discrete projections to distinct brain regions, including the nucleus accumbens (NA), that are involved in more specific aspects of memory. Indeed, the NA subregions, the core and shell, are both known to be innervated by the BLA and prior studies suggest that they may have distinct roles in memory processing related to contextual and nociceptive (e.g. footshock) learning, such as those involved in contextual fear conditioning (CFC). Therefore, to develop a better understanding of the roles of distinct BLA projections to the NA during the consolidation of different kinds of learning, we will use optogenetics to gain control over specific BLANA pathways (shell vs. core) during the immediate posttraining consolidation period. Specifically, the current proposal will utilize optogenetic stimulation or inhibition of BLANAshell vs. BLANAcore pathways to influence memory consolidation after training on a modified CFC task, in which the nociceptive or emotional stimulus (the footshock) and the context are separated, enabling experimental manipulations to selectively affect the consolidation for learning about one component and not the other. In Aim 1, we will optically stimulate the different BLANA pathways to understand their respective roles in the consolidation of context vs. footshock learning. Aim 2 will provide a complementary loss-of-function examination of these pathways by optically inhibiting the BLANA pathways immediately after training for each kind of learning. In both aims, optogenetic stimulation/inhibition will be given to each candidate pathway immediately after the relevant training to determine its role in influencing consolidation for that component of the CFC learning. These results will be the first to show that BLA inputs to different structures selectively modulate consolidation for different aspects of learning, thus enhancing our understanding of the neural connections underlying the consolidation of contextual fear conditioning and providing a critical foundation for future research.