State-dependent changes of extracellular glutamate in the medial preoptic area in freely behaving rats

doi:10.1016/0304-3940(96)12918-9

Neuroscience Letters

Volume 214, Issues 2–3, 23 August 1996, Pages 179-182

https://doi.org/10.1016/0304-3940(96)12918-9 Get rights and content

Abstract

Microdialysis technique was applied to the medial preoptic area (mPOA) of the hypothalamus, a crucial site for the regulation of sleep, in order to analyze the interrelationship between the extracellular level of glutamate (Glu) and the vigilance states. Dialysates from the mPOA were sampled at 5-min intervals for 2-h diurnal period with a perfusion rate of 2.0 μl/min in freely moving rats, whose sleep-waking behaviors were polysomnographically monitored. Extracellular Glu increased during wakefulness, exhibiting a peak at the transition period from wakefulness to non-rapid-eye-movement sleep (NREMS) (18.0% above the average), whereas it decreased during NREMS (9.2% below the average). It is likely that Glu in the mPOA is dynamically involved in the alterations of the vigilance states.

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In agreement with our present data, Chari et al. (1995) found no impact on sleep after local delivery of GABA into the mPOA [57]. Nevertheless, the role of the mPOA in the regulation of sleep has been demonstrated using different techniques [10, 16, 58-64]. However, since the protocol and doses applied for the mPOA were the same as in the VLPO, the results suggest that the GABAergic processes that control sleep in the postpartum rat are weaker within the mPOA than in the VLPO.
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Dash MB et al. showed that the concentration of glutamate in prefrontal and motor cortex increased progressively during waking and REM sleep and decreased in NREM sleep (Dash et al., 2009). Otherwise, the extracellular level of glutamate in the pedunculopontine tegmental nucleus (Kodama and Honda, 1999), the medial preoptic area (Azuma et al., 1996), and the nucleus accumbens (Lena et al., 2005) was reported to be increased during wakefulness and decreased during NREM or REM sleep. Astrocytes also play a vital role in sleep wake regulation.
Glutamate is the major excitatory neurotransmitter in the brain and plays an essential role in regulating wakefulness. Histaminergic neurons, which are exclusively localized in the tuberomammillary nucleus (TMN) of the hypothalamus, have a pivotal role in the regulation of sleep–wake patterns by sending widespread projections into many brain areas implicated in sleep–wake control. The role of glutamate in histaminergic neurons within the TMN and the resulting sleep–wake profile remains unknown. We found that glutamate, NMDA, AMPA or dihydrokainate, a glutamate-uptake inhibitor, dose-dependently increased wakefulness when microinjected into the rat TMN. Glutamate, NMDA, and AMPA also increased the firing rate of action potentials in TMN histaminergic neurons. The arousal-promoting effect of glutamate was inhibited by NMDA and histamine H₁ receptor antagonists. Furthermore, MK-801, an NMDA receptor antagonist, inhibited the firing rate of histaminergic neurons and increased non-rapid eye movement sleep after microinjection into rat TMN. Taken together, these findings demonstrated that glutamate activated histaminergic neurons in the TMN and increased wakefulness in rats, possibly via the action of NMDA and histamine H₁ receptors.
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A large body of evidence has established the role of the medial preoptic area (mPOA) in regulation of slow wave sleep (SWS). Although the mPOA neurons contain excitatory neurotransmitter glutamate, its role in sleep–wakefulness is not known. In the present study microinjection of monosodium glutamate (40, 80 and 120 ng) into the mPOA augmented SWS. Earlier reports have shown enhancement of paradoxical sleep by glutamate in other brain areas.
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Modulation of glutamate-induced outward current by prostaglandin E <inf>2</inf> in rat dissociated preoptic neurons
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Citation Excerpt :
Glutamate is a major excitatory neurotransmitter in the hypothalamus including the POA. Activation of glutamate receptors (GluRs) in the POA has been reported to modulate various physiological functions including neuroendocrine, reproduction, body temperature, and vigilance state [3,5,39]. There is compelling evidence that proinflammatory cytokines and related mediators are involved in the GluR-mediated physiological and pathological processes [1,7,8,21,28,33,35], although underlying mechanisms are not very clear.
The preoptic/anterior hypothalamus (POA) is one of the major brain regions where cytokines and their related mediators (i.e., prostaglandins) exert diverse actions. In the present study, the modulatory effects of prostaglandin E₂ (PGE₂) on the glutamate-induced membrane currents were examined using perforated-patch clamp method in rat POA neurons that had been mechanically dissociated by vibration without enzyme treatment. Application of glutamate through U-tube induced a slow outward current following fast inward ionotroic current at a holding membrane potential of −30 mV. The slow outward current was also induced by N-methyl-d-aspartate (NMDA), accompanied by an increased membrane conductance, and inhibited by perfusion with Ca²⁺-free solution, tetraethylammonium chloride (TEA), and apamin, suggesting a Ca²⁺-dependent K⁺ current (KCa) activated by Ca²⁺ entry through NMDA channels. Perfusion with PGE₂ at 0.1–10 μM, a principal mediator of fever and neuroendocrine control at the POA, did not produce apparent current by itself, but selectively potentiated the glutamate- or NMDA-induced KCa without affecting inward currents. The KCa induced by activation of NMDA receptors may serve as a feedback mechanism and the modulatory effects of PGE₂ on the KCa may have an important physiological significance.

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^∗∗: The authors are grateful to Professor Takeo Machida, Saitama University, Japan for his encouragement.

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State-dependent changes of extracellular glutamate in the medial preoptic area in freely behaving rats

Abstract

Life Sci.

Neurosci. Lett.

Alcohol

Neurosci. Lett.

Brain Res.

Behav. Brain Res.

Neuroscience