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Further studies on the monoaminergic regulation of the sleep-promoting neurones of the ventro-lateral preoptic area

English title Further studies on the monoaminergic regulation of the sleep-promoting neurones of the ventro-lateral preoptic area
Applicant Serafin Mauro
Number 102060
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2003 - 30.09.2006
Approved amount 232'440.00
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Keywords (4)

Ventrolateral preoptic area; monoamines; sleep; wakefulness

Lay Summary (English)

Lead
Lay summary
Neurons in the ventrolateral preoptic nucleus (VLPO) that contain GABA promote sleep by inhibiting neurons of the arousal systems. Reciprocally, transmitters used by these systems, including noradrenaline (NA), acetylcholine (ACh) and serotonine (5-HT), exert an inhibitory action upon the VLPO neurons (Gallopin et al., 2000, Nature 404, 992-95). Because nicotine, an agonist of ACh, acts as a potent stimulant, we queried first whether it might participate in the cholinergic inhibition of the sleep-promoting VLPO neurons. With the use of various agonists, antagonists and blockers, we demonstrated that VLPO neurons are dually inhibited by ACh through the activation of presynaptic nicotinic receptors located on noradrenergic terminals leading to the facilitation of NA release and that of postsynaptic muscarinic receptors (Saint-Mleux et al., 2004, J Neurosci 24, 63-7). Such dual complementary actions allow ACh and nicotine to enhance wakefulness by inhibiting the sleep-promoting system while facilitating other wake-promoting systems.Then to further investigate the regulation of the sleep-waking cycle we started to study first, the influence of circadian processes (1) and second, that of homeostatic processes (2) in neurons playing a key role in either sleep or wakefulness.1) Because the suprachiasmatic nucleus (SCN), the major brain circadian pacemaker, is known to influence the timing of sleep and waking, we studied the effect of SCN stimulation on VLPO neurons. Using an acute in vitro preparation of the rat anterior hypothalamus/preoptic area, we found that whereas single-pulse stimulations of the SCN evoked fast ionotropic IPSPs and EPSPs, train stimulations unexpectedly evoked a long-lasting inhibition (LLI). Such LLIs could also be evoked in VLPO neurons by pressure application of NMDA within the SCN, indicating the specific activation of SCN neurons. The LLI was shown to result from the presynaptic facilitation of NA release acting on alpha2-adrenoreceptors and to depend on the opening of a potassium conductance. These results show that the SCN can provide a LLI of the sleep-promoting VLPO neurons that could play a role in the circadian organization of the sleep-waking cycle (J Neurosci, 2007, in press). 2) Sleep deprivation (SD) is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. We hypothesized that SD, which allows investigating sleep homeostasis without circadian influences, might leave a trace in vitro in neurons playing a major role in the regulation of the sleep-waking cycle. We decided to test this possibility on wake-promoting hypocretin/orexin (hcrt/orx) neurons which are necessary to maintain alertness. We showed that, after a short 2 hours period of total sleep deprivation, the action of NA on identified hcrt/orx neurons changes from an excitation to an inhibition. We propose that such a conspicuous modification of responsiveness should contribute to the growing sleepiness that accompanies SD (Grivel et al., 2005, J Neurosci 25, 4127-30).
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
113996 Effects of sleep deprivation on wake and sleep-promoting neurons: an in vitro electrophysiological approach 01.10.2006 Project funding (Div. I-III)
59473 The ventrolateral preoptic nucleus: studies on a sleep-related area 01.04.2000 Project funding (Div. I-III)

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