A38 SLEEP, Volume 42, Abstract Supplement, 2019 A. Basic and Translational Sleep Science VI. Learning, Memory and Cognition controlling for the effect of age. This suggests that sleep spindle characteristics may be a potential biomarker of changes in cogni- tive function in this population. Support (If Any): This work was supported in part by the Canadian Sleep and Circadian Network Multi-site Mentoring Program Award (to VG) 0092 SLEEP DEPRIVATION LEADS TO FRAGMENTED MEMORY LOSS Jennifer E. Ashton, PhD, Marcus O. Harrington, PhD, Diane Langthorne, MRes, Scott A. Cairney, PhD University of York, York, United Kingdom. Introduction: Forgetting is moderated by post-learning sleep, indi- cating that newly formed memories beneft from sleep-associated consolidation. Although rates of forgetting after a single day of wakefulness are well established, how prolonged periods of sleep deprivation impact on retrieval are unclear. Moreover, whether extended sleep restriction infuences the qualitative nature of for- getting is yet to be established. In two experiments, we examined the effects of normal and protracted sleep loss on forgetting. Methods: Experiment One: 27 healthy adults (17 females, 20.85 ± 3.29 years), entered a repeated-measures study with two condi- tions (sleep and wake). In the sleep condition, learning and baseline memory assessment for adjective-image pairs took place before a night of sleep. Retrieval for the adjectives (item memory) and image categories (associative memory) was tested the following morning. In the wake condition, learning and testing took place in the morn- ing and evening, respectively. Experiment Two: 28 healthy adults (24 females, 19.43 ± 1.32 years) completed the same procedures, but the test phase occurred in the morning after a night of sleep or 24 hours sleep deprivation. In both experiments, a follow-up test was included 48 hours later to assess longer-term impacts of sleep loss on forgetting. Results: Experiment One: item forgetting was higher after wake- fulness than sleep (F(1,26)=5.67, p=.025, η 2 =.18), but there was no additional defcit in associative memory (F(1,26)=0.12, p=.73, η 2 =.01). No further differences were observed after 48 hours (p>.05). Experiment Two: item forgetting was amplifed after sleep deprivation relative to sleep (F(1,27)=20.53, p<.001, η 2 =.43). However, in contrast to normal wakefulness, extended overnight sleep loss led to a further impairment in associative memory (F(1,27)=10.30, p=.003, η 2 =.28). Moreover, a marginal increase in item forgetting was observed in the sleep deprivation condition 48 hours later (F(1,27)=3.57, p=.07, η 2 =.12). Conclusion: Item memories and their associations are lost or retained as composite representations after a normal period of wakefulness. However, prolonged sleep deprivation not only ampli- fes forgetting, but also appears to result in memory fragmentation, such that retained item memories lose their associative links. Support (If Any): Medical Research Council Career Development Award (MR/P020208/1) to S.A.C. 0093 OREXIN RECEPTOR ANTAGONISM IMPROVES STRESS- RELATED INSOMNIA, “NEXT DAY” HYPERSOMNIA, AND SLEEP DEPENDENT MEMORY CONSOLIDATION IN THE RAT James T. McKenna, PhD 1,2,3 , Mackenzie Gamble 1,2 , Marissa B. Anderson-Chernishof, MD 1,2,3 , John G. McCoy, PhD 1,4 , Robert E. Strecker, PhD 1,2,3 1 Boston VA Research Institute, Inc., Boston, MA, USA, 2 VA Boston Healthcare System, West Roxbury, MA, USA, 3 Harvard Medical School, West Roxbury, MA, USA, 4 Stonehill College, Easton, MA, USA. Introduction: Sleep facilitates learning and memory, and sleep loss/ disruption such as experienced in insomnia may impact cognition. Of utmost importance is the development of hypnotics that im- prove the sleep profle of the insomniac, but minimally impair sleep dependent memory consolidation (SDMC) and “next day” cogni- tion. Here, we evaluated if treatment in the rat with the dual orexin receptor antagonist DORA-22 (Merck & Co., Inc.) would improve insomnia-related sleep disruption, consequent hypersomnia, as well as memory impairment. Methods: To evaluate improvement of insomnia-related sleep dis- ruption, animals were frst administered doses of DORA-22 (ve- hicle 20% TPGS or DORA-22 doses of either 10, 30, or 100 mg/ kg), and then exposed to 6 hours of a dirty cage change insomnia model. Recovery period hypersomnia following model exposure was also evaluated. In a second experiment, to evaluate DORA- 22 improvement of insomnia-impaired SDMC, animals were frst trained to learn the location of a platform in the Morris Water Maze, and then administered DORA-22 (above doses), followed by insomnia model exposure. Animals were then evaluated for memory of the platform location. Results: Select doses of DORA-22 improved insomnia-related sleep disruption, producing an overall decrease in wake and in- crease in sleep. Furthermore, in the recovery period following model exposure, NREM and REM sleep latencies were decreased, indicating improved “next day” hypersomnia. Several water maze measures indicated improved probe trial performance due to DORA-22 treatment (select doses), including time and distance spent in the target quadrant and platform location, as well as number of platform crossings. Conclusion: Our rodent dirty cage change models successfully disrupted sleep, as well as produced hypersomnia and impaired sleep-dependent memory consolidation. DORA-22 treatment was hypnotically effective, including improvement of insomnia-re- lated sleep disruption and attenuated measures of hypersomnia. Additionally,DORA-22 treatment improved insomnia-associated memory consolidation defcits. Support (If Any): Merck Investigator Studies Program 0094 LOSING SLEEP AND LOSING CONTROL: SLEEP DEPRIVATION IMPAIRS MEMORY CONTROL ABILITY Marcus O. Harrington, PhD 1 , Jennifer E. Ashton, PhD 1 , Subbulakshmi Sankarasubramanian 2 , Michael C. Anderson, PhD 2 , Scott A. Cairney, PhD 1 1 Department of Psychology, University of York, York, United Kingdom, 2 MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom. Introduction: Reminders about unpleasant experiences can trigger the intrusion of unwanted memories into conscious thought. There are tremendous individual differences in the capacity for suppress- ing intrusive memories. However, the factors that govern intrusion control ability are elusive. Identifying these factors could inform our understanding of vulnerability markers for affective disorders that are characterised by intrusive thoughts. We tested the hypoth- esis that sleep might modulate our ability to prevent the past from intruding on the present. Downloaded from https://academic.oup.com/sleep/article/42/Supplement_1/A38/5451779 by guest on 24 January 2022