The rate of release of amino acids from the cerebral cortex has been measured by a surface superfusion technique in spinal (encephale isolé) cat preparations in relation to the state of cortical activation by stimulation or destruction of the midbrain reticular formation (MRF). Reticular stimulation, with desynchronized cortical activation simulating "arousal", was found to cause a selective increase three-to seven-fold (0.3 to 2.0 mμmoles/min per cm2) in the liberation of glutamic acid without significant change in glutamine, valine, and leucine, suggesting that glutamic acid may be involved either directly or indirectly in the chemical mediation of reticulo–cortical activation. Uniformly lower values were obtained during slow-wave sleep. A smaller and less consistent increase was found in aspartic acid, glycine, and taurine. Free GABA was released in the cortical superfusate in amounts ranging from 0.2 to 2.0 mμmoles/min per cm2 only during periods of slow-wave sleep or following lesions of the MRF. GABA was reduced to undetectable amounts by reticulo–cortical activation with desynchronization of the EEG, confirming previous studies showing an increase in free GABA during sleep. An increase in the rate of liberation of acetylcholine (ACh) by mesial thalamic stimulation in preparations in which the same stimulation produced no increase in glutamic acid shows that it is possible to dissociate certain of the anatomical pathways responsible for cholinergic cortical activation from those responsible for the release of glutamic acid. Quantitative comparison between the increases in ACh and glutamic acid by MRF stimulation would suggest that glutamic acid may be as important as ACh in neurochemical mechanisms underlying the reticulo–cortical arousal response, even though different release mechanisms may be involved.
The Aging Slow Wave: A Shifting Amalgam of Distinct Slow Wave and Spindle Coupling Subtypes Define Slow Wave Sleep Across the Human Lifespan