Changes in extracellular glutamate levels in rat orbitofrontal cortex during sleep and wakefulness

Functional neuroimaging studies have shown that limbic and paralimbic areas display increased activity during REM sleep when compared to wakefulness. This increase in limbic activity is specific to the REM period of sleep. PET scanners do not provide a neurochemical explanation for this increased activity during REM sleep. In order to better understand the neurochemical basis of this increase, extracellular glutamate levels were measured in the rat orbitofrontal cortex during the stages of sleep and wakefulness.

EEG and EMG activity were registered to score the behavioral state in epochs of 15 sec into three stages: wakefulness, non-REM sleep and rapid eye movement (REM) sleep. To correlate the glutamate concentration of the orbitofrontal cortex with sleep-wake states, 1-min dialysate samples were taken and classified as wakefulness, non-REM or REM sleep if all four of the 15-sec epochs occurring during the collection of that sample and after correction for dead time corresponded to the respective state. High-performance liquid chromatography (HPLC) with electrochemical detection was used to measure glutamate levels.

Glutamate levels of the orbitofrontal cortex were increased during REM sleep, diminished during wakefulness, and the lowest levels were found during non-REM sleep.

These findings demonstrate an increase in the concentration of the excitatory neurotransmitter glutamate in the orbitofrontal cortex during REM sleep, which could be related to the increased activity in paralimbic structures observed in humans using functional neuroimaging, as well as to the proposed role of REM sleep on retention of emotional memories.