Understanding memory consolidation by studying pharmacologically enhanced naps

University Of California, San Diego, La Jolla CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The primary goal of this mentored project is to prepare the candidate for a career in the investigation of the pharmacological basis of sleep-dependent memory consolidation. The training plan include: 1) gaining broad knowledge in psychopharmacology, including experimental and statistical methods for conducting pharmacology studies; 2) career development, and 3) teaching. The research plan aims to examine the mechanics of specific sleep parameters in enhancing select memory processes by pharmacologically modifying these sleep parameters during daytime sleep, or naps. Previous studies have shown that 1) a wide variety of memory improvement requires post-training nocturnal sleep, 2) these improvements have been correlated with specific sleep stages, and 3) the same memory improvements occur during naps. Further, studies suggest the neuromodulatory fluctuations related to specific sleep stages influence memory processing. New pharmacological agents, gaboxadol and zolpidem, have been shown to selectively increase specific sleep stages in nocturnal sleep. The first aim of this research is to determine the doses of gaboxadol and zolpidem that will enhance specific sleep stages in a nap. We will then apply our established methods of studying sleep-stage-specific learning in the nap to investigate whether pharmacologically enhanced naps will improve memory consolidation over non enhanced naps. We will measure these differences behaviorally, with EEG, and with functional magnetic resonance imaging (fMRI). The research proposal identifies three main thrusts to support the training plan: (1) design and implement a dose-dependent study examining the effect of pharmacological agents on sleep stages during a nap, (2) identify and analyze the relationship between dose-dependent changes in sleep stages and in drug dosage, and (3) correlate behavioral and cerebral responses to specific memory tasks produced by pharmacological intervention. These studies will lead to better understanding of the neuromodulatory mechanisms during sleep (naps) that play a role in memory consolidation processes. The research and training will form the foundation for future work in the neurobiological mechanisms underlying memory consolidation. These studies have implications for treatment of psychiatric patients and other populations with memory impairment through improved pharmacological interventions that manipulate sleep as a means of improving memory performance. [unreadable] [unreadable] [unreadable]