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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    ABSTRACT: Glutamate (Glu) is a major excitatory neurotransmitter, playing a crucial role in the functioning of the nucleus accumbens (NAc), a critical area implicated in somatosensory integration and regulation of motivated behavior. In this study, high-speed amperometry with enzyme-based biosensors was used in freely moving rats to examine changes in extracellular Glu in the NAc shell and core induced by a tone, tail pinch (TP), social interaction with a male conspecific (SI), and intravenous (iv) cocaine (1 mg/kg). To establish the contribution of Glu to electrochemical signal changes, similar recordings were conducted with null (Glu(0)) sensors, which were exposed to the same chemical and physical environment but were insensitive to Glu. TP, SI, and cocaine, but not a tone, induced relatively large and prolonged current increases detected by both Glu and Glu(0) sensors. However, current differentials revealed very rapid, much smaller, and transient increases in extracellular Glu levels, more predominantly in the NAc shell than core. In contrast to monophasic responses with natural stimuli, cocaine induced a biphasic Glu increase in the shell, with a transient peak during the injection and a slower postinjection peak. Therefore, Glu is phasically released in the NAc after exposure to natural arousing stimuli and cocaine; this release is rapid, stimulus dependent, and structure specific, suggesting its role in triggering neural and behavioral activation induced by these stimuli. This study also demonstrates the need for multiple in vitro and in vivo controls to reveal relatively small, highly phasic, and transient fluctuations in Glu levels occurring under behaviorally relevant conditions.
    Journal of Neurophysiology 04/2012; 108(1):285-99. DOI:10.1152/jn.01167.2011 · 2.89 Impact Factor
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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. "
    Sleep Disorders, 03/2012; , ISBN: 978-953-51-0293-9
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    • "The main advantage of using biosensors to monitor glutamate is temporal resolution. Glutamate biosensors have sampling rates ranging from 1 to 4 s (Dash et al. 2009, John et al. 2008). "
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    ABSTRACT: J. Neurochem. (2011) 118, 571–580. The oral part of the pontine reticular formation (PnO) is a component of the ascending reticular activating system and plays a role in the regulation of sleep and wakefulness. The PnO receives glutamatergic and GABAergic projections from many brain regions that regulate behavioral state. Indirect, pharmacological evidence has suggested that glutamatergic and GABAergic signaling within the PnO alters traits that characterize wakefulness and sleep. No previous studies have simultaneously measured endogenous glutamate and GABA from rat PnO in relation to sleep and wakefulness. The present study utilized in vivo microdialysis coupled on-line to capillary electrophoresis with laser-induced fluorescence to test the hypothesis that concentrations of glutamate and GABA in the PnO vary across the sleep/wake cycle. Concentrations of glutamate and GABA were significantly higher during wakefulness than during non-rapid eye movement sleep and rapid eye movement sleep. Regression analysis revealed that decreases in glutamate and GABA accounted for a significant portion of the variance in the duration of non-rapid eye movement sleep and rapid eye movement sleep episodes. These data provide novel support for the hypothesis that endogenous glutamate and GABA in the PnO contribute to the regulation of sleep duration.
    Journal of Neurochemistry 06/2011; 118(4):571-80. DOI:10.1111/j.1471-4159.2011.07350.x · 4.28 Impact Factor
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