Effects of acute sleep deprivation on motor and reversal learning in mice

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Highlights

  • Acute sleep deprivation impairs gains in skilled reach motor learning across time.

  • Acute sleep deprivation impairs reversal learning in a mouse skilled reaching task.

  • Acute sleep deprivation impairs reversal learning in a water-based Y-maze.

Abstract

Sleep supports the formation of a variety of declarative and non-declarative memories, and sleep deprivation often impairs these types of memories. In human subjects, natural sleep either during a nap or overnight leads to long-lasting improvements in visuomotor and fine motor tasks, but rodent models recapitulating these findings have been scarce. Here we present evidence that 5 h of acute sleep deprivation impairs mouse skilled reach learning compared to a matched period of ad libitum sleep. In sleeping mice, the duration of total sleep time during the 5 h of sleep opportunity or during the first bout of sleep did not correlate with ultimate gain in motor performance. In addition, we observed that reversal learning during the skilled reaching task was also affected by sleep deprivation. Consistent with this observation, 5 h of sleep deprivation also impaired reversal learning in the water-based Y-maze. In conclusion, acute sleep deprivation negatively impacts subsequent motor and reversal learning and memory.

Introduction

Mounting evidence supports a role for sleep in both declarative and non-declarative forms of learning and memory (Diekelmann and Born, 2010, Havekes et al., 2012). In human subjects, one of the most robust and reproducible benefits of sleep has been observed with improved motor performance as assessed through a finger tap motor sequence test (MST) (Fischer et al., 2002, Walker et al., 2002). In addition, a greater benefit of sleep was appreciated with increasing complexity of the MST (Kuriyama, Stickgold, & Walker, 2004). Disruption of sleep as a consequence of obstructive sleep apnea is associated with deficits in MST performance (Djonlagic, Saboisky, Carusona, Stickgold, & Malhotra, 2012) and in motor cortex plasticity induced by theta burst stimulation (Opie, Catcheside, Usmani, Ridding, & Semmler, 2013). Anatomically, performance of a MST after sleep preferentially activated the contralateral primary motor cortex, medial prefrontal lobe, hippocampus, and ipsilateral cerebellum (Walker, Stickgold, Alsop, Gaab, & Schlaug, 2005).

A motor learning paradigm in rodents that engages similar circuits to the MST in humans is skilled reach learning, in which an animal learns to reach through a narrow window for a sugar reward pellet (Whishaw, O’Connor, & Dunnett, 1986) with increases in accuracy over time. A previous study investigating how sleep architecture changes as a function of intensive skilled reach learning in rats showed an increase in slow wave activity in the cortex contralateral to the trained paw (Hanlon, Faraguna, Vyazovskiy, Tononi, & Cirelli, 2009); however, change in performance as a function of subsequent sleep or sleep loss was not tested. In this study, we determined the effects acute sleep deprivation mice on subsequent skilled reaching performance.

Cortical circuits mediating reversal learning may also be affected by sleep deprivation. There is evidence both supporting and refuting a role for sleep deprivation on reversal learning, depending on the exact nature of the reversal task. Because the skilled reaching task we utilized herein incorporates a form of reversal learning, we determined the effects of acute sleep deprivation on reversal learning in this task. Choice reversal in a water-based Y-maze is a behavioral task that also allows for assessment of reversal learning by training animals to locate a rescue platform in one arm of the Y-maze and subsequently testing the frequency of reversing this behavior when the rescue platform is moved to the untrained arm. The results of our studies indicate that 5 h of sleep deprivation after task acquisition impaired motor accuracy and reversal learning during skilled reaching as well as reversal learning in a water-based Y-maze.

Section snippets

Subjects

Adult C57BL/6 male mice (3–6 months of age) were kept on a 12 h/12 h light/dark schedule with lights on at 7:00 AM (zeitgeber time (ZT) 0) (8:00 AM during daylight savings). Mice were generally group housed (3–4 mice per cage) but were singly housed during skilled reach experiments. Food and water were generally available ad libitum, but food was limited during skilled reach experiments (see Section 2.3.3 below for details). All experiments were approved by the Institution of Animal Care and Use

Sleep imparts gains in motor success across time that are not achieved after acute sleep deprivation

After one week of prior acclimation to the task using the preferred paw, mice were given an initial training period using the non-preferred paw for the first time in the skilled reaching task. There were no significant differences in performance with the preferred paw either in the last three trials during the acclimation period (p = 0.23, Mann–Whitney rank sum test) or in performance during the first opportunity to use the non-preferred paw (p = 0.30, Mann–Whitney rank sum test) between mice

Discussion

In this study, we investigated the effect of 5 h acute sleep deprivation on skilled reach learning in mice, a form of motor learning that engages cortical plasticity. The vast majority of prior studies investigating relationships between sleep and motor learning have been done in human and non-human primate models. To our knowledge, this is the first study demonstrating a detrimental effect of sleep deprivation on motor learning in a rodent model.

The effect of sleep deprivation on motor learning

Acknowledgments

We thank Drs. David Rapoport and Indu Ayappa for experimental insight and critical appraisal of the manuscript and Dr. Akifumi Kishi for statistical help. This work was supported by the philanthropy of the James Kuhn Friends of Sleep Medicine, the NYU CTSA grant UL1TR000038 from the National Center for the Advancement of Translational Science (NCATS) (A.W.V), the American Sleep Medicine Foundation Physician Scientist Training Award (A.W.V.), by NIEHS Training Grant T32ES007267-20 (Principal

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