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Neuromodulation de l'activité des neurones monoaminergiques au cours du cycle veille-sommeil : Approches électrophysiologique et pharmacologique chez le rat vigile.

Abstract : The noradrenergic (NA) neurones of the Locus Coeruleus (LC) and serotonergic neurones (5HT) of the dorsal raphe nucleus (DRN) are critically involved in the control of waking and sleep states. During wakefulness, these neurones exhibit a spontaneous tonic regular firing, that progressively decreases during slow-wave sleep (SWS) and cease during paradoxical (REM) sleep (PS) (PS-off neurones). The decrease and cessation of activity of NA and 5HT neurones could be a necessary condition to enter sleep and PS. However, the mechanisms underlying the state-dependent modulation of activity of NA and 5HT neurones across the sleep-wake cycle remain unsolved.

On the basis of anatomical and electrophysiological data, we have suggested that the decrease and cessation of activity of NA LC, and 5HT DRN neurones is caused by (1) a de-activation, following the ceasing of excitatory synaptic inputs (2) auto-inhibitory mechanisms (3) an inhibitory action of adenosine (4) GABAergic and/or glycinergic afferences.
In order to test these different hypotheses, we have developed an electrophysiological and micropharmacological approach in a new experimental model of un-anaesthetised rat in a stereotaxic restraint. This pain-less and stress-less technique, has allowed us to couple extracellular unit recording of NA and 5HT neurones and micro-iontophoresis of agonists and antagonists of endogenous neurotransmitters
Our findings support the hypothesis according to which, the tonic activity of NA neurones depends upon their intrinsic pacemaker properties. The activity of 5HT neurones, in contrast, would at least in part depend upon the tonic excitation from NA neurones. We have also determined that GABA and glycine exert a tonic inhibition of NA and 5HT neurones across the sleep-wake cycle. Our results further suggest that the glycinergic inhibitory tone is constant while the GABAergic tone progressively builds up during SWS and is maximal during PS. GABA would thus be the major neurotransmitter responsible for the inactivation of NA LC neurones and 5HT DRN neurones necessary for sleep onset and PS.

Our anatomical results support the hypothesis that at least two distinct populations of GABAergic neurones are involved in the inactivation of NA and 5HT neurones during sleep. A first one, localized in the lateral and ventrolateral preoptic area would be active during SWS, and a second one, localized in the periaqueductal grey would be involved during PS.
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https://tel.archives-ouvertes.fr/tel-00369665
Contributor : Damien Gervasoni <>
Submitted on : Friday, March 20, 2009 - 5:14:00 PM
Last modification on : Monday, October 19, 2020 - 11:10:42 AM
Long-term archiving on: : Thursday, June 10, 2010 - 5:53:32 PM

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  • HAL Id : tel-00369665, version 1

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Damien Gervasoni. Neuromodulation de l'activité des neurones monoaminergiques au cours du cycle veille-sommeil : Approches électrophysiologique et pharmacologique chez le rat vigile.. Physiologie [q-bio.TO]. Université Claude Bernard - Lyon I, 2000. Français. ⟨tel-00369665⟩

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