Role of different neural pathways during memory consolidation

点击翻译按钮获取中文摘要

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.