Locus coeruleus neurons: cessation of activity during cataplexy

Wu, Ming-Fung; Gulyani, Seema; Yau, Elvina; Mignot, Emmanuel; Phan, Bao Anh; Siegel, Jerome M.

doi:10.1016/s0306-4522(98)00600-9

Cited by 202 publications

(138 citation statements)

References 49 publications

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“…In agreement with this interpretation, a significant overlap in electrophysiological findings between cataplexy and REM sleep has been reported (Siegel et al 1991;Wu et al 1999). H-reflex activity, a muscle response with monosynaptic latency due to excitation of some Ia afferents in the spinal cord, profoundly diminishes or disappears during both REM sleep and cataplexy (Guilleminault et al 1974).…”

Section: Discussionsupporting

confidence: 69%

Sulpiride, a D2/D3 Blocker, Reduces Cataplexy but not REM Sleep in Canine Narcolepsy

Okura

Riehl

Mignot

et al. 2000

Neuropsychopharmacology

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Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness (EDS), fragmented nighttime sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis (Aldrich 1992). EDS and cataplexy, "a sudden and bilateral loss of postural muscle tone in association with intense emotion" ICSD (International classification of sleep disorders ) (Diagnostic Classification Steering Committee, Thorpy MJ, Chairman 1990), are the most disabling symptoms of narcolepsy. EDS is usually treated using amphetamine-like stimulants (Aldrich 1992;Nishino and Mignot 1997). Although stimulants reduce daytime sleepiness, they have little effect on cataplexy, and thus additional anticataplectic medications are often needed in the treatment of narcolepsy. Tricyclic antidepressants have been the most commonly used anticataplectic agents since the 1960s (Akimoto et al. 1960;Aldrich 1992;Nishino and Mignot 1997). However, tricyclics have a variety of pharmacological effects, such as anticholinergic and antihistaminergic effects and/or alpha-1 adrenergic antagonism (Baldessarini 1983). Some of these effects are responsible for a variety of side effects during chronic treatment (dry mouth, tachycardia, weight gain, sexual dysfunction, sedation, and orthostatic hypotension) (Guilleminault 1994;Thorpy and Goswami 1990). Tricyclics also significantly affect nocturnal sleep by suppressing REM sleep, increasing muscle tone and inducing nocturnal movements (Guilleminault 1994). The long-term impact of chronically disturbing sleep in narcoleptic patients due to these compounds is unknown.Canine narcolepsy is a naturally occurring animal model which presents behavioral, pharmacological and electrophysiological similarities to the human disorder Sulpiride, aD2/D3 Blocker, in Narcoleptic Dogs 529 (Baker and Dement 1985;Kaitin et al. 1986;Nishino and Mignot 1997). Narcoleptic dogs manifest a short sleep latency, fragmented sleep patterns, and cataplexy (Kaitin et al. 1986;Nishino et al. 1999). It was recently discovered that mutations in the gene encoding a receptor for hypocretins (also called orexins) induces genetic narcolepsy in Dobermans and Labradors (Lin et al. 1999). Subsequently, it was also found that cerebrospinal fluid hypocretin-1 levels are low in human narcoleptic subjects, indicating that a deficit in hypocretin neurotransmission is also involved in human narcolepsy (Nishino et al. 2000b). Thus, the use of the canine model to uncover the pathophysiology of narcolepsy and to develop new treatments for human narcolepsy is further warranted. Previous pharmacological studies in canine narcolepsy have demonstrated that decreased monoaminergic transmission is one of the most important factors in the pathophysiology of narcolepsy (Mignot et al. 1989;Nishino et al. 1990;Nishino and Mignot 1997;Reid et al. 1998). Inactivation of catecholaminergic transmission aggravates cataplexy and/or induces sleep in these animals [see (Nishino and Mignot 1997)]. We further identified several catecholaminergic receptor subtypes specifically i...

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Section: Discussionsupporting

confidence: 69%

Sulpiride, a D2/D3 Blocker, Reduces Cataplexy but not REM Sleep in Canine Narcolepsy

Okura

Riehl

Mignot

et al. 2000

Neuropsychopharmacology

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“…a 1 -Receptors, which are known to excite neurons in most other brain regions (Nicoll et al, 1990), are believed to excite LC neurons as well based on the findings that pharmacological blockade of a 1 -receptors either in brain slices from adult rats (Ivanov and Aston-Jones, 1995) or in vivo in awake dogs (Wu et al, 1999) significantly reduces resting LC unit firing rate by approximately 50%. a 1 -Agonists also produce attenuation of a 2 -adrenoceptorinduced hyperpolarization and GIRK-induced conductance in LC neurons in brain slices (Osborne et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle

Yang

Vaca

Stone

2006

Neuropsychopharmacol

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The present experiments were undertaken to clarify the role of central a 1 -adrenoceptors in reward processes. Rats, trained to selfstimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered a 1 -selective drugs near the locus coeruleus (LC), a site of a dense concentration of a 1 -receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC a 1 -receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the a 1 -agonist, phenylephrine and were not attributable to terazosin's weak action at a 2 -adrenoceptors. It is concluded that LC a 1 -adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment. Neuropsychopharmacology (2007) 32, 835-841.

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“…Another potential and very potent source of a waking glutamatergic drive could be from the dopaminergic, noradrenergic, and serotonergic cell groups that promote arousal and facilitate motor activity (Wu et al, 1999;Jacobs et al, 2002;Lu et al, 2006). These monoaminergic cells not only exhibit a wake-active discharge pattern, project to and excite motoneurons, but they also synthesize and corelease glutamate (for example, 86% of noradrenergic cells in the locus ceruleus coexpress glutamate) (Liu et al, 1995).…”

Section: What Is the Source Of The Endogenous Glutamatergic Drive To mentioning

confidence: 99%

An Endogenous Glutamatergic Drive onto Somatic Motoneurons Contributes to the Stereotypical Pattern of Muscle Tone across the Sleep–Wake Cycle

Burgess¹,

et al. 2008

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Skeletal muscle tone is modulated in a stereotypical pattern across the sleep-wake cycle. Abnormalities in this modulation contribute to most of the major sleep disorders; therefore, characterizing the neurochemical substrate responsible for transmitting a sleep-wake drive to somatic motoneurons needs to be determined. Glutamate is an excitatory neurotransmitter that modulates motoneuron excitability; however, its role in regulating motoneuron excitability and muscle tone during natural sleep-wake behaviors is unknown. Therefore, we used reverse-microdialysis, electrophysiology, pharmacological, and histological methods to determine how changes in glutamatergic neurotransmission within the trigeminal motor pool contribute to the sleep-wake pattern of masseter muscle tone in behaving rats. We found that blockade of non-NMDA and NMDA glutamate receptors (via CNQX and D-AP-5) on trigeminal motoneurons reduced waking masseter tone to sleeping levels, indicating that masseter tone is maximal during alert waking because motoneurons are activated by an endogenous glutamatergic drive. This wake-related drive is switched off in non-rapid eye movement (NREM) sleep, and this contributes to the suppression of muscle tone during this state. We also show that a functional glutamatergic drive generates the muscle twitches that characterize phasic rapid-eye movement (REM) sleep. However, loss of a waking glutamatergic drive is not sufficient for triggering the motor atonia that characterizes REM sleep because potent activation of either AMPA or NMDA receptors on trigeminal motoneurons was unable to reverse REM atonia. We conclude that an endogenous glutamatergic drive onto somatic motoneurons contributes to the stereotypical pattern of muscle tone during wakefulness, NREM sleep, and phasic REM sleep but not during tonic REM sleep.

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Locus coeruleus neurons: cessation of activity during cataplexy

Cited by 202 publications

References 49 publications

Sulpiride, a D2/D3 Blocker, Reduces Cataplexy but not REM Sleep in Canine Narcolepsy

Sulpiride, a D2/D3 Blocker, Reduces Cataplexy but not REM Sleep in Canine Narcolepsy

Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle

An Endogenous Glutamatergic Drive onto Somatic Motoneurons Contributes to the Stereotypical Pattern of Muscle Tone across the Sleep–Wake Cycle

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