Enhanced Slow-Wave EEG Activity and Thermoregulatory Impairment following the Inhibition of the Lateral Hypothalamus in the Rat

Abstract

Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be the consequence of the inhibition of specific neuronal populations within the LH, i.e. the orexin and the MCH neurons, respectively. However, the interpretation of these results is limited by the lack of quantitative analysis of the electroencephalographic (EEG) activity that is critical for the assessment of NREM sleep quality and the presence of aborted NREM-to-REM sleep transitions. Furthermore, the lack of evaluation of the autonomic and thermoregulatory effects of the treatment does not exclude the possibility that the wake-sleep changes are merely the consequence of the autonomic, in particular thermoregulatory, changes that may follow the inhibition of LH neurons. In the present study, the EEG and autonomic/thermoregulatory effects of a prolonged LH inhibition provoked by the repeated local delivery of the GABAA agonist muscimol were studied in rats kept at thermoneutral (24°C) and at a low (10°C) ambient temperature (Ta), a condition which is known to depress sleep occurrence. Here we show that: 1) at both Tas, LH inhibition promoted a peculiar and sustained bout of NREM sleep characterized by an enhancement of slow-wave activity with no NREM-to-REM sleep transitions; 2) LH inhibition caused a marked transitory decrease in brain temperature at Ta 10°C, but not at Ta 24°C, suggesting that sleep changes induced by LH inhibition at thermoneutrality are not caused by a thermoregulatory impairment. These changes are far different from those observed after the short-term selective inhibition of either orexin or MCH neurons, suggesting that other LH neurons are involved in sleep-wake modulation.

Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors

“…We observed that PWScr m+/pmutant mice present a high body temperature, coupled with an increase and lack of appropriate thermoregulatory responses. Thermoregulation is tightly integrated with the regulation of sleep and is also controlled by OX neuromodulation (37,49). For example, narcoleptic subjects exhibit a paradoxically lower core body temperature while awake (50) and a higher body temperature during sleep (51,52).…”

A Novel Population of Wake-Promoting GABAergic Neurons in the Ventral Lateral Hypothalamus

“… Summary The largest synaptic input to the sleep-promoting ventrolateral preoptic area (VLPO) [1] arises from the lateral hypothalamus [2], a brain area associated with arousal [3–5]. However, the neurochemical identity of the majority of these VLPO-projecting neurons within the LH, as well as their function in the arousal network, remains unknown.…”

Paternally expressed imprintedSnord116andPeg3regulate hypothalamic orexin neurons

“…We observed that PWScr m+/pmutant mice present a high body temperature coupled with an increase and lack of appropriate thermoregulatory responses. Thermoregulation is tightly integrated with the regulation of sleep and is also controlled by OX neuromodulation [34,49]. For example, narcoleptic subjects exhibit a paradoxical lower core body temperature while awake [50] and a higher body temperature during sleep [51,52].…”