• Giancarlo Vanini, Ralph Lydic, and Helen A Baghdoyan.
• Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
• Sleep. 2012 Oct 1; 35 (10): 1325-34.

Study ObjectivesGABAergic and cholinergic transmission within the basal forebrain and cerebral cortex contribute to the regulation of sleep and wakefulness. In contrast to levels of acetylcholine (ACh), levels of endogenous GABA in basal forebrain and cortex during sleep and wakefulness have not previously been quantified. This study (1) tested the hypothesis that there are differential, state-specific changes in GABA levels within the substantia innominata (SI) region of the basal forebrain and somatosensory cortex; and (2) quantified the ratio of GABAergic to cholinergic transmission in the SI, cortex, and pontine reticular formation during rapid eye movement sleep (REM), non-REM sleep (NREM), and wakefulness.DesignWithin/between subjects.SettingUniversity of Michigan.Patients Or ParticipantsAdult, male, purpose bred cats (n = 5).InterventionsIn vivo microdialysis, high performance liquid chromatography, electrophysiological recordings.Measurements And ResultsIn the SI, GABA levels were significantly greater during NREM (17%) than during REM. In the cortex, GABA levels were significantly greater during NREM than during wakefulness (39%) and REM (63%). During prolonged wakefulness, there was a linear increase in cortical GABA levels, and the amount of time spent awake accounted for 87% of the variance in GABA. The GABA-to-ACh ratio was largest during NREM for all brain regions. REM was characterized by a 68% decrease in the GABA-to-ACh ratio across brain regions, always due to a decrease in GABA levels.ConclusionThree of the brain regions that comprise the anatomically distributed, sleep-generating network have in common a GABA-mediated, sleep-dependent decrease in the GABA-to-ACh ratio.

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