Corrigendum: Image discrimination reversal learning is impaired by sleep deprivation in rats: Cognitive rigidity or fatigue?

[This corrects the article DOI: 10.3389/fnsys.2022.1052441.].

Image discrimination reversal learning is impaired by sleep deprivation in rats: Cognitive rigidity or fatigue?

Introduction: Insufficient sleep is pervasive worldwide, and its toll on health and safety is recapitulated in many settings. It is thus important to understand how poor sleep affects the brain and decision making. A robust literature documents the adverse effects of sleep deprivation on cognitive processes including cognitive flexibility, which is the capacity to appraise new feedback and make behavioral adjustments to respond appropriately. Animal models are often used to unravel the molecules, genes and neural circuits that are altered by sleep loss. Herein we take a translational approach to model the effects of sleep deprivation on cognitive rigidity, i.e., impaired cognitive flexibility in rats. Methods: There are several approaches to assess cognitive rigidity; in the present study, we employ a pairwise discrimination reversal task. To our knowledge this is the first time this paradigm has been used to investigate sleep deprivation. In this touchscreen operant platform, we trained rats to select one of two images to claim a sucrose pellet reward. If the non-rewarded image was selected the rats proceeded to a correction trial where both images were presented in the same position as before. This image presentation continued until the rat selected the correct image. Once rats reached performance criteria, the reward contingencies were reversed. In one group of rats the initial reversal session was preceded by 10 h of sleep deprivation. We compared those rats to controls with undisturbed sleep on the number of sessions to reach performance criteria, number of trials per session, response latencies, correct responses, errors, perseverative errors and perseveration bouts in the initial training and reversal phases. Results: We report that on reversal session one, sleep deprived rats completed a fraction of the trials completed by controls. On subsequent reversal sessions, the sleep deprived rats struggled to adapt to the reversed contingencies despite completing a similar number of trials, suggesting an effect of cognitive rigidity separate from fatigue. Discussion: We discuss the delayed performance dynamics incurred by sleep loss in the context of fatigue and the implications of using pairwise discrimination reversal as a model to further examine the effects of sleep loss on adaptive decision making.

The rat Lux Actuating Search Task (LAST) and effects of sleep deprivation on task reversal performance.

Sleep deprivation (SD) causes significant deficits in multiple aspects of cognition, including sustained attention and working memory. Investigating the neural processes underpinning these cognitive losses has proven challenging due to the confounds of current animal tasks; many employ appetitive or aversive stimuli to motivate behavior, while others lack task complexity that translates to human studies of executive function. We established the Lux Actuating Search Task (LAST) to circumvent these issues. The LAST is performed in a circular, open-field arena that requires rats to find an unmarked, quasi-randomly positioned target. Constant low-level floor vibrations motivate ambulation, while light intensity (determined by the rodent's proximity to the target destination) provides continuous visual feedback. The task has two paradigms that differ based on the relationship between the light intensity and target proximity: the Low Lux Target (LLT) paradigm and the High Lux Target paradigm (HLT). In this study, on days 1-6, the rats completed nine trials per day on one of the two paradigms. On day 7, the rats were either sleep deprived by gentle handling or were left undisturbed before undertaking the opposite (reversal) paradigm on days 7-9. Our results showed that SD significantly impeded the ability of Long Evans rats to learn the reversal paradigm, as indicated by increased times to target and increased failure percentages compared to rats whose sleep was undisturbed. Rats also showed reduced learning with the HLT paradigm, as the initial task or as the reversal task, likely due to the rodents' photophobia limiting their motivation to navigate toward a bright light, which is required to succeed.

Floor vibrations for motivation and feedback in the rat vibration actuating search task.

Motivating rodents to perform cognitive tasks often relies on the application of aversive stimuli. The Vibration Actuating Search Task (VAST) is a novel open-field task in which gradient floor vibration provides motivation for the rodent to navigate in the direction of diminishing vibration to an unmarked target destination. Using floor vibration as a motivational stimulus may overcome several of the potential confounds associated with stimuli used in other tasks. In a series of three experiments, we determined whether (1) rats exhibit place preference for floor vibration over other aversive stimuli (i.e., water, foot shock, and bright light), (2) exposure to floor vibration is associated with a lower corticosterone response than exposure to these other stimuli, (3) rats successfully acquire the VAST, and (4) VAST performance is sensitive to 6 h of sleep deprivation (SD). Our results showed that rats exhibited place preference for vibration over water, foot shock, and bright light environments, and that corticosterone levels were lower in rats exposed to vibration than those exposed to water. VAST performance also significantly improved over two days of testing for some metrics, and SD impaired VAST performance. Overall, we conclude that (1) rats exhibit place preference for vibration over other stimuli commonly used to motivate task performance, (2) the vibrations employed by the VAST produce lower concentrations of circulating corticosterone than forced swimming, (3) rats can learn to use gradient floor vibration as a mode of performance feedback within two days of testing, and (4) VAST performance is substantially impaired by SD. Thus, the VAST is an effective and practical testbed for studying the mechanisms by which SD causes deficits in feedback-dependent decision making.

A Role for Astroglial Calcium in Mammalian Sleep and Sleep Regulation.

Mammalian sleep expression and regulation have historically been thought to reflect the activity of neurons. Changes in other brain cells (glia) across the sleep-wake cycle and their role in sleep regulation are comparatively unexplored. We show that sleep and wakefulness are accompanied by state-dependent changes in astroglial activity. Using a miniature microscope in freely behaving mice and a two-photon microscope in head-fixed, unanesthetized mice, we show that astroglial calcium signals are highest in wake and lowest in sleep and are most pronounced in astroglial processes. We also find that astroglial calcium signals during non-rapid eye movement sleep change in proportion to sleep need. In contrast to neurons, astrocytes become less synchronized during non-rapid eye movement sleep after sleep deprivation at the network and single-cell level. Finally, we show that conditionally reducing intracellular calcium in astrocytes impairs the homeostatic response to sleep deprivation. Thus, astroglial calcium activity changes dynamically across vigilance states, is proportional to sleep need, and is a component of the sleep homeostat.

Performance on the mouse vibration actuating search task is compromised by sleep deprivation.

As we go about our daily routines we are continuously bombarded with environmental feedback that requires appraisal and response. Sleep loss can compromise the efficiency by which these cognitive processes function. Operationally, poor performance caused by insufficient sleep translates to increased health and safety risks in settings where attention and timely and/or accurate decisions to respond are critical (e.g., at work, on the road, etc.). Current rodent tasks that assess altered cognition after sleep deprivation (SD) do not accurately model the continuous multisensory feedback that informs goal-oriented behavior in humans. Herein, we describe the vibration actuating search task (VAST), which consists of a vibrating open field with pseudo-randomly selected entrance and target destination points. To successfully complete a trial, mice use feedback from rotary motor-induced floor vibrations to navigate from the entrance point to the target destination. Sets of 20 trials were conducted on 3 consecutive days, and before testing on the third day control mice were undisturbed while other mice were sleep deprived for 10 h. On the first 2 days mice learned the task with high success rates. Alternatively, VAST performance was compromised following SD as measured by increased failures in task completion, time to target, time spent immobile, and decreased speed as compared with undisturbed mice. The VAST enables the analysis of continuous feedback via multiple sensory modalities in mice and is applicable to a variety of operational settings.NEW & NOTEWORTHY The vibration actuating search task (VAST) is a novel performance assay that uses continuous auditory and haptic feedback to motivate and direct search behaviors in mice. The VAST is rapidly acquired by mice and performance is disrupted by sleep deprivation. The VAST has practical application in occupational settings. The cognitive aspects of the sensorimotor integration in the VAST may prove useful for rodent models of neurodegenerative disease.