Enhanced slow-wave EEG activity and thermoregulatory impairment following the inhibition of the lateral hypothalamus in the rat

PLoS One. 2014 Nov 14;9(11):e112849. doi: 10.1371/journal.pone.0112849. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Brain / pathology
  • Cold Temperature
  • Electroencephalography*
  • Electromyography
  • GABA-A Receptor Agonists / pharmacology
  • Heart Rate
  • Hypothalamic Area, Lateral / drug effects
  • Hypothalamic Area, Lateral / pathology
  • Hypothalamic Area, Lateral / physiology*
  • Male
  • Muscimol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / chemistry
  • Receptors, GABA-A / metabolism
  • Sleep Stages / drug effects
  • Sleep Stages / physiology
  • Sleep, REM / drug effects
  • Sleep, REM / physiology
  • Wakefulness / drug effects
  • Wakefulness / physiology


  • GABA-A Receptor Agonists
  • Receptors, GABA-A
  • Muscimol

Grants and funding

This work has been supported by the grant PRIN 2008FY7K9S from the Ministero dell’Istruzione, dell’Università e della Ricerca (http://www.istruzione.it)- Italy (RA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.