Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep states in the mouse.
ABSTRACT 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 (<10 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.
SourceAvailable from: Antoine Adamantidis[Show abstract] [Hide abstract]
ABSTRACT: Besides the master clock located in the suprachiasmatic nucleus (SCN) of the brain, additional clocks are distributed across the central nervous system and the body. The role of these 'secondary' clocks remains unclear. A new study shows that the lack of an internal clock in histamine neurons profoundly perturbs sleep. Copyright © 2015 Elsevier Ltd. All rights reserved.Current Biology 01/2015; 25(1):R49-51. DOI:10.1016/j.cub.2014.11.022 · 9.92 Impact Factor
04/2015, Degree: Ph D; Doctoral Thesis; Fren; Université Claude Bernard de Lyon, France, Supervisor: Jan-Sheng Lin, Patricia Franco, Rubens Reimão
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ABSTRACT: Circadian clocks allow anticipation of daily environmental changes . The suprachiasmatic nucleus (SCN) houses the master clock, but clocks are also widely expressed elsewhere in the body . Although some peripheral clocks have established roles , it is unclear what local brain clocks do [2, 3]. We tested the contribution of one putative local clock in mouse histaminergic neurons in the tuberomamillary nucleus to the regulation of the sleep-wake cycle. Histaminergic neurons are silent during sleep, and start firing after wake onset [4-6]; the released histamine, made by the enzyme histidine decarboxylase (HDC), enhances wakefulness [7-11]. We found that hdc gene expression varies with time of day. Selectively deleting the Bmal1 (also known as Arntl or Mop3 ) clock gene from histaminergic cells removes this variation, producing higher HDC expression and brain histamine levels during the day. The consequences include more fragmented sleep, prolonged wake at night, shallower sleep depth (lower nonrapid eye movement [NREM] δ power), increased NREM-to-REM transitions, hindered recovery sleep after sleep deprivation, and impaired memory. Removing BMAL1 from histaminergic neurons does not, however, affect circadian rhythms. We propose that for mammals with polyphasic/nonwake consolidating sleep, the local BMAL1-dependent clock directs appropriately timed declines and increases in histamine biosynthesis to produce an appropriate balance of wake and sleep within the overall daily cycle of rest and activity specified by the SCN. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.