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

Cerri M, Del Vecchio F, Mastrotto M, Luppi M, Martelli D, Perez E, Tupone D, Zamboni G, Amici R - PLoS ONE (2014)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and NeuroMotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.

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.

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Tail temperature.The figure shows the average tail temperature measured from 9∶50 to 10∶00 (approximately 1 hour before the first injection) and from 11∶50 and 12∶00 (approximately 1 hour after the first injection of either muscimol (black bar) or saline (white bar)) at ambient temperature (Ta) = 24°C (on the left) or at Ta = 10°C (on the right). Data are shown as mean ± SEM. * = p<0.05.
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pone-0112849-g006: Tail temperature.The figure shows the average tail temperature measured from 9∶50 to 10∶00 (approximately 1 hour before the first injection) and from 11∶50 and 12∶00 (approximately 1 hour after the first injection of either muscimol (black bar) or saline (white bar)) at ambient temperature (Ta) = 24°C (on the left) or at Ta = 10°C (on the right). Data are shown as mean ± SEM. * = p<0.05.

Mentions: At Ta 24°C, the repeated injection of saline produced a significant increase in Tbrain compared to that observed during the injections of muscimol (peak: 37.8±0.3°C, t*(192) = 5.20, p<0.05) (Figure 5). At Ta 10°C, saline injection still produced an increase in Tbrain, while muscimol injections evoked a decrease in Tbrain, that reached a nadir of 35.5±0.2°C (t*(240) = 8.42, p<0.05 compared to saline) after 3 hours. Tbrain returned rapidly towards physiological levels, but it remained significantly higher compared to the saline group for the rest of the day. No significant differences were observed in the recovery period. The decrease in Tbrain was not caused by an increase in thermal dissipation, since the tail did not show any sign of vasodilation, but, rather, a modest but significant vasoconstriction (Figure 6), dropping from an average pre-injection value of 12.8±1.1°C to 11.8±1.1°C one hour after the first injection (t(6) = 2.59, p<0.05). A significant reduction in Ttail was also observed at Ta 24°C, when Ttail dropped from an average pre-injection value of 31.1±0.3°C to 29.6±0.2°C one hour after the first injection (t(4) = 8.48, p<0.05). The latter value was also significantly lower (p<0.05) compared to that observed one hour after the first saline injection (31.5±0.4°C; t(5) = 3.55).


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

Cerri M, Del Vecchio F, Mastrotto M, Luppi M, Martelli D, Perez E, Tupone D, Zamboni G, Amici R - PLoS ONE (2014)

Tail temperature.The figure shows the average tail temperature measured from 9∶50 to 10∶00 (approximately 1 hour before the first injection) and from 11∶50 and 12∶00 (approximately 1 hour after the first injection of either muscimol (black bar) or saline (white bar)) at ambient temperature (Ta) = 24°C (on the left) or at Ta = 10°C (on the right). Data are shown as mean ± SEM. * = p<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232523&req=5

pone-0112849-g006: Tail temperature.The figure shows the average tail temperature measured from 9∶50 to 10∶00 (approximately 1 hour before the first injection) and from 11∶50 and 12∶00 (approximately 1 hour after the first injection of either muscimol (black bar) or saline (white bar)) at ambient temperature (Ta) = 24°C (on the left) or at Ta = 10°C (on the right). Data are shown as mean ± SEM. * = p<0.05.
Mentions: At Ta 24°C, the repeated injection of saline produced a significant increase in Tbrain compared to that observed during the injections of muscimol (peak: 37.8±0.3°C, t*(192) = 5.20, p<0.05) (Figure 5). At Ta 10°C, saline injection still produced an increase in Tbrain, while muscimol injections evoked a decrease in Tbrain, that reached a nadir of 35.5±0.2°C (t*(240) = 8.42, p<0.05 compared to saline) after 3 hours. Tbrain returned rapidly towards physiological levels, but it remained significantly higher compared to the saline group for the rest of the day. No significant differences were observed in the recovery period. The decrease in Tbrain was not caused by an increase in thermal dissipation, since the tail did not show any sign of vasodilation, but, rather, a modest but significant vasoconstriction (Figure 6), dropping from an average pre-injection value of 12.8±1.1°C to 11.8±1.1°C one hour after the first injection (t(6) = 2.59, p<0.05). A significant reduction in Ttail was also observed at Ta 24°C, when Ttail dropped from an average pre-injection value of 31.1±0.3°C to 29.6±0.2°C one hour after the first injection (t(4) = 8.48, p<0.05). The latter value was also significantly lower (p<0.05) compared to that observed one hour after the first saline injection (31.5±0.4°C; t(5) = 3.55).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and NeuroMotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.

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.

Show MeSH
Related in: MedlinePlus