Brainstem structures responsible for paradoxical sleep onset and maintenance.

This paper is dedicated to our mentor, Michel Jouvet who inspired our career and transmitted to us his passion for the study of the mechanisms responsible for paradoxical sleep genesis and also that of its still mysterious functions. We expose in the following the progresses in the knowledge in this field brought during 40 years by Michel Jouvet and his team and more recently by the members of a new CNRS laboratory in which we aim to pursue in the path opened by Michel Jouvet.

Localization of the GABAergic and non-GABAergic neurons projecting to the sublaterodorsal nucleus and potentially gating paradoxical sleep onset.

We recently determined in rats that iontophoretic application of bicuculline or gabazine [two GABAa antagonists] and kainic acid (a glutamate agonist) in the sublaterodorsal nucleus (SLD) induces with a very short latency a paradoxical sleep-like state. From these results, we proposed that GABAergic and glutamatergic inputs to the SLD paradoxical sleep (PS)-executive neurons gate the onset of PS [R. Boissard et al.

The rat ponto-medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study.

The neuronal network responsible for paradoxical sleep (PS) onset and maintenance has not previously been identified in the rat, unlike the cat. To fill this gap, this study has developed a new technique involving the recording of sleep-wake states in unanaesthetized head-restrained rats whilst locally administering pharmacological agents by microiontophoresis from glass multibarrel micropipettes, into the dorsal pontine tegmentum and combining this with functional neuroanatomy. Pharmacological agents used for iontophoretic administration included carbachol, kainic acid, bicuculline and gabazine.

Effect of chronic treatment with milnacipran on sleep architecture in rats compared with paroxetine and imipramine.

A number of studies in humans and various other species have shown that chronic treatment with antidepressants, such as tricyclics or selective serotonin reuptake inhibitors (SSRIs), induces a decrease or suppression of rapid eye movement (REM) sleep. The effect of a new selective serotonin and noradrenaline reuptake inhibiting (SNRI) antidepressant, milnacipran, on REM sleep has been investigated and compared with that of the SSRI, paroxetine, and the tricyclic, imipramine. Rats injected with vehicle or milnacipran twice a day showed, over 24 h, a similar amount of REM sleep, number and duration of REM sleep episodes to control rats.

Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons.

Extracellular electrophysiological recordings in freely moving cats have shown that serotonergic neurons from the dorsal raphe nucleus (DRN) fire tonically during wakefulness, decrease their activity during slow wave sleep (SWS), and are nearly quiescent during paradoxical sleep (PS). The mechanisms at the origin of the modulation of activity of these neurons are still unknown. Here, we show in the unanesthetized rat that the iontophoretic application of the GABA(A) antagonist bicuculline on dorsal raphe serotonergic neurons induces a tonic discharge during SWS and PS and an increase of discharge rate during quiet waking.

Production and characterization of a new specific antiserum against the taurine putative biosynthetic enzyme cysteine sulfinate decarboxylase.

We have shown previously that cysteine sulfinate decarboxylase (CSD), the putative biosynthetic enzyme of taurine in the brain, is identical to the liver enzyme according to biochemical, kinetic, and immunochemical criteria. In the present work, CSD was purified in its native form from rat liver. The purification was performed in eight steps, which included conventional chromatography (diethylaminoethyl cellulose, hydroxylapatite), followed by HPLC (hydrophobic, adsorption, and ion-exchange HPLC).

Central noradrenergic reactivity to stress in Maudsley rat strains.

Maudsley reactive (MR) and Maudsley nonreactive (MNRA) rats were submitted to a single session of acute 5-min immobilization stress and immediately sacrificed by decapitation. Subsequent neurochemical analysis revealed an elevation of 3,4-dihydroxyphenylacetic acid levels in the locus coeruleus and in the ventrolateral medulla, but not in the dorsomedial medulla, of rats of the two strains compared with nonstressed controls. This response was greater in the MR than in the MNRA group, suggesting a strain difference in the reactivity of the central noradrenergic cells to acute stress.

Long-term isolation of Wistar rats alters brain monoamine turnover, blood corticosterone, and ACTH.

In this work, we investigated neurochemical parameters in the brain of male Wistar rats after isolation times (13 weeks) longer than those previously reported with this strain: a large majority of animals became muricidal under these conditions. Changes in monoamines turnover in hippocampus, cortex, and cerebellum and, in the blood, ACTH, and corticosterone were investigated. Monoamine turnover was analysed using two different approaches: first, by measuring neurotransmitter and metabolite levels and second, by measuring rate of accumulation of the precursor after decarboxylase.

Differential early time course activation of the brainstem catecholaminergic groups in response to various stresses.

The effects of various stressors (restraint, ether, histamine and insulin-induced hypoglycemia stress) on the early time course activation of the different catecholaminergic (CA) cell groups A1/C1, A2/C2 and locus ceruleus (LC) from the brainstem were studied. The activity of the central noradrenergic neurons was assessed by measuring in tissue punches the 3,4-dihydroxyphenylacetic acid (DOPAC) level, a side metabolite of noradrenaline (NA) and adrenaline biosynthesis that is thought to reflect the activity of NA cells. Short 5 min restraint stress led to an immediate increase of DOPAC level in the three CA groups.