Sleep deprivation impairs object recognition in mice

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Abstract

Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in an object recognition task in OF1 mice subjected to 6 h SD either immediately after the acquisition phase (0–6 SD) or 6 h later (7–12 SD), and in corresponding undisturbed controls. Motor activity was continuously recorded with infrared sensors. All groups explored two familiar, previously encountered objects to a similar extent, both at the end of the acquisition phase and 24 h later during the test phase, indicating intact familiarity detection. During the test phase 0–6 SD mice failed to discriminate between the single novel and the two familiar objects. In contrast, the 7–12 SD group and the two control groups explored the novel object significantly longer than the two familiar objects. Plasma corticosterone levels determined after SD did not differ from time-matched undisturbed controls, but were significantly below the level measured after learning alone. ACTH did not differ between the groups. Therefore, it is unlikely that stress contributed to the memory impairment. We conclude that the loss of sleep and the activities the mice engaged in during the SD, impaired recognition memory retrieval, when they occurred immediately after acquisition. The delayed SD enabled memory consolidation during the 6 h when the mice were allowed to sleep, and had no detrimental effect on memory. Neither SD schedule impaired object familiarity processing, suggesting that only specific cognitive abilities were sensitive to the intervention. Sleep may either actively promote memory formation, or alternatively, sleep may provide optimal conditions of non-interference for consolidation.

Introduction

There is increasing evidence that sleep may be important for learning and memory, whereas a sleep deficit results in performance impairment both in rodents and humans (for review Stickgold, 2005, Walker, 2004). However, the role of sleep in memory formation is complex and appears to depend on the nature of the task (e.g., Graves, Heller, Pack, & Abel, 2003). Moreover, there are data indicating that sleep should occur within a specific time window following upon the training or acquisition phase in order to facilitate learning effectively (e.g., Pearlman, 1973, Smith and Butler, 1982, Smith et al., 1991). Thus, 4 h of REM sleep deprivation immediately following training resulted in learning impairment in the hidden platform of the Morris water maze, but not in the visual platform (Smith & Rose, 1996). The same duration of REM sleep deprivation performed after acquisition in the eight-arm radial maze task resulted in a deficit of spatial reference memory, whereas working memory was intact (Smith, Conway, & Rose, 1998). Recent data show that Fisher rats deprived from REM sleep for 4 h after training, switch from a spatial to a non-spatial strategy to solve a complex associative learning task (Bjorness, Riley, Tysor, & Poe, 2005). Moreover, 5 h total sleep deprivation in C57BL/6 mice impaired contextual but not cued fear conditioning, when the SD was scheduled immediately after the acquisition phase (Graves et al., 2003). In contrast, delayed REM sleep deprivation (hours 4–8, 8–12 or 13–24 after acquisition) or delayed total sleep deprivation (hours 5–10) had no effect on memory (Bjorness et al., 2005, Graves et al., 2003, Smith and Rose, 1996, Smith et al., 1998). Taken together, these data indicate that sleep at the appropriate time, may facilitate and optimize memory formation of certain tasks. On the other hand, the fundamental relevance of sleep in memory processing has been questioned (reviewed in Coenen, 2005, Doyon et al., 2005, Korman et al., 2005, Schredl, 2005, Siegel, 2005, Vertes, 2004, Vertes, 2005, Vertes and Siegel, 2005). Important arguments are the specificity of the tasks that seem to profit from sleep, contrasting a global role of sleep in memory consolidation, and the limitations of comparing results obtained in humans and animals.

The one-trial object recognition task, originally developed for rats (Ennaceur & Delacour, 1988) and applied in several mouse studies (e.g., Dodart et al., 1997, Genoux et al., 2002), provides a useful behavioral paradigm to investigate the effects of sleep loss on memory consolidation and retrieval. Animals have to learn to recognize biologically meaningless objects or their spatial location, and should be able to retrieve the object or location information in a complex spatial scene when tested 24 h later. It was suggested that memories of objects in rodents can be compared to human episodic-like memory (Dere et al., 2004, Morris, 2001).

To our knowledge the role of sleep on recognition memory has not been investigated in rats or mice. Therefore, it is unknown whether there is a specific timing of sleep that may be more important for consolidation or retention of recognition memories. To test whether undisturbed sleep occurring immediately after learning is critical and sufficient for consolidation of object recognition, we subjected mice to 6 h total SD by “gentle handling” either immediately (0–6 SD) or 6 h after the end of an acquisition phase (7–12 SD).

Sleep deprivation has been considered to be stressful for animals (Horne & McGrath, 1984). Since stress may be a cause for memory impairment, we measured the plasma levels of the stress hormones corticosterone and ACTH in mice subjected to acquisition alone and in mice subjected to acquisition followed by SD. To evaluate the effectiveness of SD and the effects of learning and SD on rest, motor activity was recorded with infrared (IR) sensors for several days before the learning task and throughout the experimental days.

Section snippets

Animals

The Cantonal Veterinary Office of Zürich approved all experimental procedures. The experiments were performed in OF1 mice because a detailed analysis of their sleep and the effects of 5 h sleep deprivation were reported recently (Kopp, Petit, Magistretti, Borbély, & Tobler, 2002) and OF1 mice have been used in similar object recognition tests (Bour, Little, Dodart, Kelche, & Mathis, 2004). Adult male outbred OF1 mice (n = 89), weighing 41 ± 5 g (SD), were kept individually in Macrolon cages (36 × 20 × 35 

Object recognition in the complex scene in OF1 mice

During the acquisition phase, the two control groups explored each of the three objects to the same extent [‘object’ F (2, 30) = 0.77, ‘group’ F (1, 15) = 1.63, ‘object × group’ F (2, 30) = 0.01] and displayed a reduction in their exploration [Fig. 2A; ‘session: 1 vs. 5’ F (1, 15) = 8.67, p < .006, ‘group’ F (1, 15) = 0.13, ‘group × session’ F (1, 15) = 0.04].

During the test phase (Fig. 2B), both control groups spent more time exploring the novel object compared to the two familiar objects [p < .05 Tukey test after two-way

Discussion

A period of sleep deprivation following immediately upon an acquisition phase caused a significant retrieval detriment in a complex spatial scene paradigm 24 h later. This deficit in object discrimination was restricted to the group of mice subjected to SD during the first 6 h following acquisition, since both the controls that were allowed to sleep, as well as the mice subjected to a similar but delayed SD had no such deficit (Fig. 2C). Apparently, only the early intervention interfered with the

Acknowledgments

We thank members of the group for their help during the SD. This work was supported by the Swiss National Science Foundation Grants No. 3100-053005.97/2 and 3100A0-100567/1 and EU Grant STREP-518189.

References (55)

  • M. Hotte et al.

    Modulation of recognition and temporal order memory retrieval by dopamine D(1) receptor in rats

    Neurobiology of Learning and Memory

    (2005)
  • C. Kopp et al.

    Comparison of the effects of modafinil and sleep deprivation on sleep and cortical EEG spectra in mice

    Neuropharmacology

    (2002)
  • K. Louie et al.

    Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep

    Neuron

    (2001)
  • S. Palchykova et al.

    Sleep deprivation and daily torpor impair object recognition in Djungarian hamsters

    Physiology & Behavior

    (2006)
  • C. Pearlman

    REM sleep deprivation impairs latent extinction in rats

    Physiology & Behavior

    (1973)
  • G.R. Poe et al.

    Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep

    Brain Research

    (2000)
  • C. Smith et al.

    Paradoxical sleep at selective times following training is necessary for learning

    Physiology & Behavior

    (1982)
  • C. Smith et al.

    Evidence for a paradoxical sleep window for place learning in the Morris water maze

    Physiology & Behavior

    (1996)
  • C.T. Smith et al.

    Brief paradoxical sleep deprivation impairs reference, but not working, memory in the radial arm maze task

    Neurobiology of Learning and Memory

    (1998)
  • R.P. Vertes

    Memory consolidation in sleep; dream or reality

    Neuron

    (2004)
  • O.T. Wolf

    HPA axis and memory

    Best Practice & Research. Clinical Endocrinology & Metabolism

    (2003)
  • T.E. Bjorness et al.

    REM restriction persistently alters strategy used to solve a spatial task

    Learning & Memory

    (2005)
  • A. Coenen

    Where is the classic interference theory for sleep and memory?

    Behavioral and Brain Sciences

    (2005)
  • S. Datta

    Avoidance task training potentiates phasic pontine-wave density in the rat: A mechanism for sleep-dependent plasticity

    Journal of Neuroscience

    (2000)
  • A.S. Dave et al.

    Song replay during sleep and computational rules for sensorimotor vocal learning

    Science

    (2000)
  • E. Dere et al.

    Higher order memories for objects encountered in different spatio-temporaral contexts in mice: Evidence for episodic memory

    Reviews in the Neurosciences

    (2004)
  • J.C. Dodart et al.

    Scopolamine-induced deficits in a two-trial object recognition task in mice

    Neuroreport

    (1997)
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