These findings indicate that extracellular lactate concentration is a reliable sleep/wake biomarker and can be used independently of the EEG signal.

We report on electroencephalograph (EEG) and electromyograph (EMG) measurements concurrently with real-time changes in L-glutamate concentration. These data reveal a link between sleep state and extracellular neurotransmitter changes in a freely-moving (tethered) mouse. This study reveals, for the first time in mice, that the extracellular L-glutamate concentration in the pre-frontal cortex (PFC) increases during periods of extended wakefulness, decreases during extended sleep episodes and spikes during periods of REM sleep. Individual sleep epochs (10 s in duration) were scored as wake, slow-wave (SW) sleep or rapid eye movement (REM) sleep, and then correlated as a function of time with measured changes in L-glutamate concentrations. The observed L-glutamate levels show a statistically significant increase of 0.86 ± 0.26 μM (p < 0.05) over 37 wake episodes recorded from all mice (n = 6). Over the course of 49 measured sleep periods longer than 15 min, L-glutamate concentrations decline by a similar amount (0.88 ± 0.37 μM, p < 0.08). The analysis of 163 individual REM sleep episodes greater than one min in length across all mice (n = 6) demonstrates a significant rise in L-glutamate levels as compared to the 1 min preceding REM sleep onset (RM-ANOVA, DF = 20, F = 6.458, p < 0.001). The observed rapid changes in L-glutamate concentration during REM sleep last only between 1 and 3 min. The approach described can also be extended to other regions of the brain which are hypothesized to play a role in sleep. This study highlights the importance of obtaining simultaneous measurements of neurotransmitter levels in conjunction with sleep markers to help elucidate the underlying physiological and ultimately the genetic components of sleep.

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Second by second measurement of neurochemicals such as glutamate, glucose and lactate in the brain using electrochemical biosensors is a powerful tool that has been used to profile concentration changes due to pharmacological and behavioral interactions. Now this ability to measure metabolic changes in targeted regions of the brain has been integrated with a very low‐noise, turn‐key electroencephalograph (EEG) recording system.As an example of this system's strength, male C57 mice were simultaneously implanted with an intracerebral guide cannula targeting the prefrontal cortex and electrodes to measure cortical EEG. Real‐time, second by second measurements of glucose levels and EEG activity were recorded over a 24 hour period. Results showed that glucose levels in mice transitioning from waking to slow‐wave sleep rose an average of 116 ± 27.0 uM (n =57 episodes). Conversely, glucose levels in mice transitioning from sleep to wakefulness resulted in an average decrease of 121 ± 27.0 uM glucose. (n=54 episodes). Additional data will be presented demonstrating the system being used to monitor changes of neurotransmitters during normal sleep and periods of sleep deprivation.Funding through NIH SBIR Grant #5R44MH076318‐03.