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, CA 91343, USA.
AJP Regulatory Integrative and Comparative Physiology (Impact Factor: 3.11). 10/2008; 295(6):R2041-9. DOI: 10.1152/ajpregu.90541.2008
Source: PubMed


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.

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Available from: Lalini Ramanathan, Aug 18, 2014
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    • "For example, a rapid, ϳ86 ␮M jump in Glu levels was reported in the striatum at the start of TP in awake rats (Rutherford et al. 2007). Relatively large fluctuations in [Glu] (ϳ1–10 ␮M) were also reported in the cortex after spontaneous transitions within the sleep-wake cycle (Dash et al. 2009; John et al. 2008; Naylor et al. 2011) and in the NAc shell after a systemic injection of MK-801, a noncompetitive NMDA antagonist (Uslaner et al. 2011). In contrast, with simultaneous two-sensor (Glu-Glu 0 ) recordings, only ϳ25–35 nM phasic increases in [Glu] were detected during breathing in the medulla of anesthetized rats (Gourine at al. 2008 "
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    • "On the other side, sleep terrors occur more often in children than in adults, while children have more delta sleep (Pinel, 2009; Lee & Douglass, 2010). Another recent animal study (John et al., 2008) showed a rapid increase in the glutamate level during REM sleep and awakening in the histamine-containing posterior hypothalamic region and the perifornical-lateral hypothalamus, and its reduction shortly after the termination of REM sleep and awakening. In the animal study of Dash and colleagues conducted in 2009, which employed a very sensitive method (in vivo amperometry) to measure cortical extracellular glutamate, a progressive increase was observed in the cortical extracellular glutamate concentration during REM sleep and waking. "

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