Automated sleep scoring in rats and mice using the naive Bayes classifier.

We describe a new simple MATLAB-based method for automated scoring of rat and mouse sleep using the naive Bayes classifier. This method is highly sensitive resulting in overall auto-rater agreement of 93%, comparable to an inter-rater agreement between two human scorers (92%), with high sensitivity and specificity values for wake (94% and 96%), NREM sleep (94% and 97%) and REM sleep (89% and 97%) states. In addition to baseline sleep-wake conditions, the performance of the naive Bayes classifier was assessed in sleep deprivation and drug infusion experiments, as well as in aged and transgenic animals using multiple EEG derivations. 24-h recordings from 30 different animals were used, with approximately 5% of the data manually scored as training data for the classification algorithm.

Nitric oxide mediated recovery sleep is attenuated with aging.

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in the cholinergic basal forebrain (BF) during sleep deprivation (SD) is implicated in adenosine (AD) release and induction of recovery sleep. Aging is associated with impairments in sleep homeostasis, such as decrease in non-rapid eye movement sleep (NREM) intensity following SD. We hypothesized that age related changes in sleep homeostasis may be induced by impairments in NO-mediated sleep induction. To test this hypothesis we measured levels of NO and iNOS in the BF during SD as well as recovery sleep after SD and NO-donor (DETA/NO) infusion into the BF in three age groups of rats (young, 4 months; middle-aged, 14 months; old, 24 months). We found that in aged rats as compared to young (1) recovery NREM sleep intensity was significantly decreased, (2) neither iNOS nor NO increased in the BF during SD, and (3) DETA/NO infusion failed to induce sleep. Together, these results support our hypothesis that aging impairs the mechanism through which NO in the BF induces sleep.

Basal forebrain lactate release and promotion of cortical arousal during prolonged waking is attenuated in aging.

The wake-promoting basal forebrain (BF) is critically involved in sustaining cortical arousal. In the present study, we investigated how aging affects the capacity of the BF to cope with continuous activation during prolonged waking. Increased neuronal activity induces lactate release in the activated brain area, and BF stimulation increases cortical arousal. We used in vivo microdialysis to measure lactate levels in the BF, and electroencephalography (EEG) to measure cortical arousal, during 3 h sleep deprivation (SD) in three age groups of rats. Lactate increased during SD in young but not in aged (middle-aged and old) rats. The increase in high-frequency (HF) EEG theta power (7-9 Hz), a marker of cortical arousal and active waking, was attenuated in the aged. Furthermore, a positive correlation between BF lactate release and HF EEG theta increase was found in young but not in aged rats. We hypothesized that these age-related attenuations result from reduced capacity of the BF to respond to increased neuronal activation. This was tested by stimulating the BF with glutamate receptor agonist NMDA. Whereas BF stimulation increased waking in young and old rats, lactate increase and the HF EEG theta increase were attenuated in the old. Also, the homeostatic increase in sleep intensity after SD was attenuated in aged rats. Our results suggest that an age-related attenuation in BF function reduces cortical arousal during prolonged waking. As the quality of waking is important in regulating the subsequent sleep, reduced cortical arousal during SD may contribute to the age-related reduction in sleep intensity.