Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats

Neurobiology Research (151A3), Veterans Affairs Greater Los Angeles Health Care System, North Hills; and Department of Psychiatry and Brain Research Institute, University of California at Los Angeles, Los Angeles, California Submitted 30 June 2008 ; accepted in final form 22 September 2008 The histamine-containing posterior hypothalamic region (PH-TMN) plays a key role in sleep-wake regulation. We investigated rapid changes in glutamate release in the PH-TMN across the sleep-wake cycle with a glutamate biosensor that allows the measurement of glutamate levels at 1- to 4-s resolution. In the PH-TMN, glutamate levels increased in active waking (AW) and rapid eye movement (REM) sleep compared with quiet waking and nonrapid eye movement (NREM) sleep. There was a rapid (0.6 ± 1.8 s) and progressive increase in glutamate levels at REM sleep onset. A reduction in glutamate levels consistently preceded the offset of REM sleep by 8 ± 3 s. Short-duration sleep deprivation resulted in a progressive increase in glutamate levels in the PH-TMN, perifornical-lateral hypothalamus (PF-LH), and cortex. We found that in the PF-LH, glutamate levels took a longer time to return to basal values compared with the time it took for glutamate levels to increase to peak values during AW onset. This is in contrast to other regions we studied in which the return to baseline values after AW was quicker than their rise with waking onset. In summary, we demonstrated an increase in glutamate levels in the PH-TMN with REM/AW onset and a drop in glutamate levels before the offset of REM. High temporal resolution measurement of glutamate levels reveals dynamic changes in release linked to the initiation and termination of REM sleep. rapid eye movement sleep; histamine; microdialysis; biosensor; cortex Address for reprint requests and other correspondence: J. M. Siegel, UCLA/Neurobiology Research (151A3), 16111 Plummer St., Sepulveda VAMC, 16111 Plummer St., North Hills, CA 91343 (e-mail: JSiegel{at}UCLA.edu )