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

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

High-frequency oscillations recorded in human medial temporal lobe during sleep.

The presence of fast ripple oscillations (FRs, 200-500 Hz) has been confirmed in rodent epilepsy models but has not been observed in nonepileptic rodents, suggesting that FRs are associated with epileptogenesis. Although studies in human epileptic patients have reported that both FRs and ripples (80-200 Hz) chiefly occur during non-rapid eye movement sleep (NREM), and that ripple oscillations in human hippocampus resemble those found in nonprimate slow wave sleep, quantitative studies of these oscillations previously have not been conducted during polysomnographically defined sleep and waking states. Spontaneous FRs and ripples were detected using automated computer techniques in patients with medial temporal lobe epilepsy during sleep and waking, and results showed that the incidence of ripples, which are thought to represent normal activity in animal and human hippocampus, was similar between epileptogenic and nonepileptogenic temporal lobe, whereas rates of FR occurrence were significantly associated with epileptogenic areas. The generation of both FRs and ripples showed the highest rates of occurrence during NREM sleep. During REM sleep, ripple rates were lowest, whereas FR rates remained elevated and were equivalent to rates observed during waking. The predominance of FRs within the epileptogenic zone not only during NREM sleep, but also during epileptiform-suppressing desynchronized episodes of waking and REM sleep supports the view that FRs are the product of pathological neuronal hypersynchronization associated with seizure-generating areas.