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记忆相关障碍至关重要，如恐惧症和创伤后应激障碍(PTSD)。此前研究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，尽管这些连接在调节不同方面或形式的记忆方面可能很重要。这种关注在一定程度上是由于技术上的限制；然而，光遗传学的出现改变了我们在这方面的能力，使光学能够以时间和空间的精度控制神经通路。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路径的活动。具体地说，我们将关注杏仁基底核(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调节的，包括伏隔核(NA)，这些区域涉及记忆的更具体方面。事实上，NA亚区，即核心和外壳，都已知受到BLA的支配，先前的研究表明，它们可能在与情境和伤害性(如足底电击)学习有关的记忆加工中扮演着不同的角色，例如参与情境恐惧条件反射(CFC)的记忆加工。因此，为了更好地理解不同类型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在训练后立即巩固期间获得对特定BLANA途径(外壳与核心)的控制。具体地说，目前的建议将利用光遗传刺激或抑制BLANAShell与BLAN在修改的CFC任务训练后影响记忆巩固的通路，在该任务中，伤害性或情绪刺激(足电击)和背景是分开的，使实验操作能够选择性地影响学习一个成分而不是另一个成分的巩固。在目标1中，我们将光刺激不同的BLANA路径，以了解它们在巩固情境与脚部电击学习中的各自角色。目标2将通过在每种学习训练后立即光学抑制BLANA通路来提供这些通路的补充性功能丧失检查。在这两个目标中，将在相关培训后立即对每个候选途径给予光遗传刺激/抑制，以确定其在影响氟氯化碳学习的这一部分的巩固方面的作用。这些结果将首次表明，BLA对不同结构的输入选择性地调节学习的不同方面的巩固，从而加强我们对语境恐惧条件作用巩固的神经联系的理解，并为未来的研究提供关键的基础。

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.