Cataplexy-Active Neurons in the Hypothalamus

John, Joshi; Wu, Ming-Fung; Boehmer, Lisa; Siegel, Jerome M.

doi:10.1016/s0896-6273(04)00247-8

Cited by 199 publications

(60 citation statements)

References 60 publications

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“…Thus, local slow waves in layer 4 of primary areas may be facilitated by the high ratio between acetylcholine and noradrenaline. The absence of other neuromodulators could also contribute, such as orexin or histamine [30]. However, orexinergic and histaminergic projections mainly target deep layers and at least for orexin, post-synaptic signaling seems to be confined to layer 6 [31, 32].…”

Section: Resultsmentioning

confidence: 99%

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

et al. 2016

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Summary Sleep is traditionally constituted of two global behavioral states, NREM and REM, characterized by quiescence and reduced responsiveness to sensory stimuli [1]. NREM sleep is distinguished by slow waves and spindles throughout the cerebral cortex, REM sleep by an ‘activated’, low-voltage fast EEG paradoxically similar to that of wake, accompanied by rapid eye movements and muscle atonia. However, recent evidence has shown that cortical activity patterns during wake and NREM sleep are not as global as previously thought. Local slow waves can appear in various cortical regions in both awake humans [2] and rodents [3-5]. Intracranial recordings in humans [6] and rodents [4, 7] have shown that NREM sleep slow waves most often involve only a subset of brain regions that varies from wave to wave rather than occurring near-synchronously across all cortical areas. Moreover, some cortical areas can transiently ‘wake up’ [8] in an otherwise sleeping brain. Yet, until now, cortical activity during REM sleep was thought to be homogenously wake-like. We show here, using local laminar recordings in freely moving mice, that slow waves occur regularly during REM sleep, but only in primary sensory and motor areas, and mostly in layer 4, the main target of relay thalamic inputs, and in layer 3. This finding may help explain why during REM sleep we remain disconnected from the environment even though the bulk of the cortex shows wakelike, paradoxical activation.

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Section: Resultsmentioning

confidence: 99%

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

et al. 2016

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“…Although the activity of human HA TM neurons remains unknown, presumed HA TM neurons in cats and dogs are reported to display a highly arousalspecific neuronal activity similar to that seen in mice (VanniMercier et al, 1985;Sakai et al, 1990;John et al, 2004). An increase in histaminergic transmission enhances W, whereas its blockade causes somnolence (for review, see Lin, 2000).…”

Section: Characteristics Of Ha Tm Neurons In Vitro and In Vivomentioning

confidence: 98%

“…In the present in vivo experiments in nonanesthetized, head-restrained mice, HA TM neurons were completely quiescent during both the drowsy state and sleep, and, during waking states, displayed a tonic (Ͻ 10 Hz) but irregular firing pattern, as shown by the large coefficient of variation for the spike interval (CV Ͼ 0.5), suggesting that mouse HA TM neurons are very sensitive to changes in vigilance level and various synaptic inputs. In this regard, mouse HA TM neurons differ from those in the cat and dog, in which presumed HA TM neurons are reported to fall silent only during deep SWS and PS (Vanni-Mercier et al, 1985;Sakai et al, 1990;John et al, 2004). Steininger et al (1999) recently reported the presence of PS (REM)-off neurons in the rat posterior hypothalamus, including the ventrolateral subgroup of the TM.…”

Section: Characteristics Of Ha Tm Neurons In Vitro and In Vivomentioning

confidence: 99%

Neuronal Activity of Histaminergic Tuberomammillary Neurons During Wake–Sleep States in the Mouse

Takahashi¹,

Lin²,

Sakai³

2006

J. Neurosci.

304

228

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Using extracellular single-unit recordings alone and in combination with neurobiotin juxtacellular labeling and histamine immunohistochemistry, we have identified, for the first time in nonanesthetized, head-restrained mice, histamine neurons in the tuberomammillary nuclei of the posterior hypothalamus. They are all characterized by triphasic broad action potentials. They are active only during wakefulness, and their activity is related to a high level of vigilance. During waking states, they display a slow (Ͻ10 Hz) tonic, repetitive, irregular firing pattern. Their activity varies in the different waking states, being lowest during quiet waking, moderate during active waking, and highest during attentive waking. They cease firing during quiet waking before the onset of EEG synchronization, the EEG sign of sleep (drowsy state), and remain silent during slow-wave sleep and paradoxical (or rapid eye movement) sleep. They exhibit a pronounced delay in firing during transitions from sleep to wakefulness or remain quiescent during the same transitions if the animals are not fully alert. They either respond with a long delay, or do not respond, to an arousing stimulus if the stimulus does not elicit an overt alert state. These data support the view that the activity of histaminergic tuberomammillary neurons plays an important role, not in the induction of wakefulness per se, but in the maintenance of the high level of vigilance necessary for cognitive processes. Conversely, cessation of their activity may play an important role in both the initiation and maintenance of sleep.

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“…Cataplexy is probably generated by an imbalance of neuronal activity: histaminergic cells fire at a level similar to wakefulness, whereas serotonergic and noradrenergic cells decrease activity. 208) First hints at the role of the histaminergic system on maintaining waking state in the CNS were provided by the occurrence of unwanted sedative effects after administration of classical H 1 R antihistamines. Based on the early work of Economo there is evidence for distinct histamine-connected wake promoting areas in the posterior hypothalamus and regions in the preoptic area associated with sleep.…”

Section: )mentioning

confidence: 99%

Histamine H3 Receptor Antagonists Go to Clinics

Sander

Kottke

Stark

2008

Biological & Pharmaceutical Bulletin

185

118

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INTRODUCTIONThe biogenic amine histamine, 2-(1H-imidazol-4-yl)-ethanamine, is produced by decarboxylation of L-histidine and is implicated in a wide range of physiological and pathophysiological functions. It is metabolised by histamine N tmethyltransferase (HMT) and mono-or diaminoxidase. Histamine is mainly acting via four distinct metabotropic histamine receptor subtypes (H 1 R-H 4 R), which have meanwhile all been cloned. Whereas antagonists for H 1 R and H 2 R subtypes have been blockbusters in therapy of allergy and ulcer, respectively, antagonists for H 3 R and H 4 R subtypes are not on the market. The recently described H 4 R seems to be involved in inflammatory and immunomodulatory processes. H 3 Rs play a central role in neurotransmission of histamine and in control of many other neurotransmitters. Several antagonists are in preclinical and some in clinical stage of development. PHARMACOLOGICAL BACKGROUND Auto-and HeteroreceptorThe H 3 R was first described in 1983 as a presynaptic autoreceptor, which mediates synthesis of histamine and inhibition of its release from histaminergic neurons in slices of rat cerebral cortex. 1) Localisation studies in rodents show a predominance in distinct regions of the central nervous system (CNS) as the H 3 R is mainly located in cerebral cortex, hippocampus, amygdala, nucleus accumbens, globus pallidus, striatum, and hypothalamus 2-5) ( Fig. 1). In addition, it is expressed in the peripheral nervous system, e.g. in gastrointestinal tract, airways and cardiovascular system. 6) Molecular aspects of the receptor, [7][8][9][10] structure-activity relationships (SAR) of ligands, [11][12][13][14][15][16][17][18][19] and pharmacology [20][21][22][23][24][25][26] have recently been resumed in many excellent reviews. This contribution focuses on the development of clinical candidates and the multifaceted potential indications targeted.In mammalian brain histaminergic neurons originate in the tuberomammillary nucleus (TMN) spreading into above mentioned brain regions, where they control histamine levels by regulation of synthesis and liberation rates 27) and modulate different neuronal systems. 28) H 3 R expression is not solely restricted to histaminergic neurons: due to its function as a heteroreceptor it can be found on colocalised neurons, and H 3 R activation modulates the release of various important neurotransmitters, i.e. dopamine, [29][30][31][32][33] acetylcholine, [34][35][36][37] norepinephrine, 38,39) serotonin, 40,41) GABA, [42][43][44] glutamate, 45) and substance P. [46][47][48] Therefore, histaminergic neurons and the cross-linkage between major neurotransmitter systems are involved in many (patho)physiological brain functions, including vigilance, memory processes, feeding behaviour and locomotor activity (Fig. 2). Interneuron cross-talk and adaptive processes seem to be important factors in H 3 Rmediated signalling. Molecular AspectsThe human histamine H 3 receptor (hH 3 R) cDNA firstly described 1999 encodes a 445 amino acid protein and belongs to the his...

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Cataplexy-Active Neurons in the Hypothalamus

Cited by 199 publications

References 60 publications

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

Neuronal Activity of Histaminergic Tuberomammillary Neurons During Wake–Sleep States in the Mouse

Histamine H3 Receptor Antagonists Go to Clinics

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