Glutamic acid stimulation of the perifornical-lateral hypothalamic area promotes arousal and inhibits non-REM/REM sleep

doi:10.1016/j.neulet.2008.05.042

Neuroscience Letters

Volume 439, Issue 3, 18 July 2008, Pages 281-286

https://doi.org/10.1016/j.neulet.2008.05.042 Get rights and content

Abstract

The orexinergic neurons, localized in the perifornical hypothalamic area (PeF), are active during waking and quiet during non-rapid eye movement (non-REM) and REM sleep. Orexins promote arousal and suppress non-REM and REM sleep. Although in vitro studies suggest that PeF-orexinergic neurons are under glutamatergic influence, the sleep–wake behavioral consequences of glutamatergic activation of those neurons are not known. We examined the effects of bilateral glutamatergic activation of neurons in and around the PeF on sleep–wake parameters in freely behaving rats. Nine male Wistar rats were surgically prepared for electrophysiological sleep–wake recording and with bilateral guide cannulae targeting the PeF for microinjection. The sleep–wake profiles of each rat were recorded for 8 h under baseline (without injection), and after bilateral microinjections of 200 nl saline and 200 nl saline containing 20 or 40 ng of l-glutamic acid (GLUT) using a remote-controlled pump and without disturbing the animals. The injection of 40 ng GLUT into the PeF (n = 6) significantly increased mean time spent in waking (F = 85.11, p < 0.001) and concomitantly decreased mean time spent in non-REM (F = 19.67, p < 0.001) and REM sleep (F = 38.72, p < 0.001). The increase in waking and decreases in non-REM and REM sleep were due to significantly increased durations of waking episodes (F = 24.64; p < 0.001) and decreased durations of non-REM (F = 12.96; p = 0.002) and REM sleep events (F = 13.82; p = 0.001), respectively. These results suggest that the activation of neurons in and around the PeF including those of orexin neurons contribute to the promotion of arousal and suppression of non-REM and REM sleep.

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Acknowledgement

Funding from Department of Biotechnology, India is acknowledged.

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The PeF-LH has been implicated in the regulation of several physiological functions, including arousal, locomotor activity and cognition (Hurley & Johnson, 2014). Stimulation of the PeF-LH evokes locomotor activity, electroencephalogram activation, and behavioral arousal (Alam & Mallick, 2008; Sinnamon, Karvosky, & Ilch, 1999; Stock, Rupprecht, Stumpf, & Schlor, 1981). Neurochemically, the PeF-LH is heterogeneous and includes neuronal groups expressing glutamate, orexin and GABA (Abrahamson, Leak, & Moore, 2001; Bittencourt et al., 1992; Gerashchenko & Shiromani, 2004; Ohno & Sakurai, 2008; Peyron et al., 1998).
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In an effort-based decision task, PeF-LH inactivation led to decrease in high reward choice. Similarly, in a delay-based decision task animals’ preference changed to a low but immediately available reward. This was not caused by a spatial memory or motor deficit. PeF-LH inactivation modified decision behavior. The results imply that PeF-LH is important for allowing the animal to pay a cost to acquire greater rewards.

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Glutamic acid stimulation of the perifornical-lateral hypothalamic area promotes arousal and inhibits non-REM/REM sleep

Abstract

Section snippets

Acknowledgement

Brain Res.

Neuroscience

Neuroscience

Neuron

Neuroscience

Neuron

Neuroscience

Neurosci. Res.

Behav. Brain Res.

Neuron

Neuroscience

Sleep–waking discharge patterns of neurons recorded in the rat perifornical lateral hypothalamic area

J. Physiol.

Orexins (hypocretins) directly excite tuberomammillary neurons

Eur. J. Neurosci.

Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons

J. Neurosci.

Promotion of sleep by targeting the orexin system in rats, dogs and humans

Nat. Med.