Glutamate as an excitatory neurotransmitter in the central nervous system, participate in initiation and maintaining of sleep and wakefulness. The paper presents an overview of the research progress of glutamate in the regulation of sleep and wakefulness, especially focuses on its role in the brainstem, lateral hypothalamus and basal forebrain. Glutamate in the brain stem regulates the brain activity and maintains muscle tone during the wakefulness, as well as adjusts the electroencephalograph (EEG) in rapid eye movement phase and leads to muscle weakness. Glutamate in the lateral hypothalamus participates in the lateral hypothalamic arousal system by activating orexins neurons. The basal forebrain glutamatergic neurons take part in EEG synchronization and cause the decrease of sleep. Finally,The glutamatergic neurons of the cerebral cortex is not just a target of the arousal system, but itself contribute to regulation of arousal. Meantime, the glutamatergic neurons can regulate sleep stages through interaction with other types of neurons, which forms a complex sleep-wake regulation network in the brain. These indicate that the switches between different phases of sleep and wakefulness have different neuronal circuits.So we also reviewed the neuronal circuits and mechanisms that glutamate may be involved in. This review will help us to get a better understanding of the roles of glutamate in sleep and wakefulness.
Glutamic Acid ; physiology ; Humans ; Sleep ; physiology ; Wakefulness ; physiology

The parabrachial nucleus (PBN) integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing, emotion, and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem. However, the precise identity and function of distinct PBN subpopulations are still largely unknown. Here, we leveraged molecular characterization, retrograde tracing, optogenetics, chemogenetics, and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain, rather than the medulla. Their activation induces freezing and anxiety-like behaviors, which in turn result in tachypnea. In addition, optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture. We propose that these neurons comprise a PBN subpopulation with specific gene expression, connectivity, and function, which play essential roles in behavioral and physiological regulation.
Parabrachial Nucleus/physiology* ; Wakefulness/physiology* ; Neurons/physiology* ; Emotions ; Sleep

The results of previous studies on the menstrual-related sleep changes were inconsistent. The menstrual-related circadian sleep-wake and rest-activity rhythms changes are still uncertain. Using actigraphic monitoring of wrist activity, we investigated the sleep-wake and rest-activity patterns of 12 normally cyclic healthy women during reproductive life. Multivariate analyses were performed during the four phases of the menstrual cycle: menstrual phase (lst to 5th day of menstrual cycle), late follicular/peri-ovulation phase (11th to 15th day), early to mid luteal phase (18th to 23rd day) and late luteal phase (25th to 28th day), respectively. The variables of circadian sleep-wake pattern were similar in the four phases, except an increased tendency of the sleep latency in peri-ovulation phase compared with the early to mid-luteal phase (19+/-18 vs 9+/-6), but unfortunately no statistical significance were found (P<0.10). Concerning the circadian patterning of rest and activity, the interdaily stability (IS) in menstrual phase was significantly higher than the early to mid luteal phase (P<0.05). In early to mid luteal phase, the M10 onset time was significantly earlier compared with that of the late follicular/peri-ovulation phase (P<0.05), and the cosinor peak time was significantly earlier compared with that of the late luteal phase (P<0.05). The circadian periodogram calculated the period length of the rhythm of average woman. The average length was (24.01+/-0.29) h, and there was no significant difference among the four menstrual phases. The results suggest that the phase of circadian rest-activity rhythm may be modulated by the menstrual cycle, but the quantity and quality of the rest-activity rhythm have no essential different, and that menstrual cycle may have no effects on the circadian sleep-wake rhythm in normally cyclic healthy women.
Activity Cycles ; physiology ; Circadian Rhythm ; Female ; Humans ; Luteal Phase ; physiology ; Menstrual Cycle ; physiology ; Sleep ; physiology ; Wakefulness ; physiology

OBJECTIVETo study the features of interictal epileptiform discharges (IED) during sleep and wakefulness in children with epilepsy.

METHODSThe polysomnography, active EEG and video EEG were performed on 48 children with epilepsy during the whole night, and wakefulness of pre- and post-sleep. The epileptiform sharp/spike discharge indexes during sleep and wakefulness were recorded. The positive rate of IED in focal and generalized epilepsy was compared.

RESULTSOf the 48 patients, 25 showed IED, including 9 cases (36.0%) in the generalized seizure group and 16 cases (64.0%) in the focal seizure group (P<0.05). The epileptiform sharp/spike discharge indexes in the whole non-rapid eye movement (NREM) sleep stage (stages S1-S4: 21.13+/-19.96, 19.59+/-17.76, 22.85+/-18.99, and 20.37+/-16.63) were significantly higher than that in the wakefulness stage (8.20+/-6.21) (P<0.05). The discharge index in the S3 stage during NREM sleep was higher than that during the rapid eye movement (REM) sleep (22.85+/-18.99 vs 12.91+/-10.95; P<0.05).

CONCLUSIONSThe positive rate of IED in the focal seizure group was higher than that in the generalized seizure group. Sleep, especially NREM sleep, facilitates IED in children with epilepsy.

Child ; Child, Preschool ; Electroencephalography ; Epilepsy ; physiopathology ; Humans ; Polysomnography ; Sleep ; physiology ; Wakefulness ; physiology

This study aims to explore the auditory response characteristics of the thalamic reticular nucleus (TRN) in awake mice during auditory information processing, so as to deepen the understanding of TRN and explore its role in the auditory system. By in vivo electrophysiological single cell attached recording of TRN neurons in 18 SPF C57BL/6J mice, we observed the responses of 314 recorded neurons to two kinds of auditory stimuli, noise and tone, applied to mice. The results showed that TRN received projections from layer six of the primary auditory cortex (A1). Among 314 TRN neurons, 56.05% responded silently, 21.02% responded only to noise and 22.93% responded to both noise and tone. The neurons with noise response can be divided into three patterns according to their response time: onset, sustain and long-lasting, accounting for 73.19%, 14.49% and 12.32%, respectively. The response threshold of the sustain pattern neurons was lower than those of the other two types. Under noise stimulation, compared with A1 layer six, TRN neurons showed unstable auditory response (P < 0.001), higher spontaneous firing rate (P < 0.001), and longer response latency (P < 0.001). Under tone stimulation, TRN's response continuity was poor, and the frequency tuning was greatly different from that of A1 layer six (P < 0.001), but their sensitivity to tone was similar (P > 0.05), and TRN's tone response threshold was much higher than that of A1 layer six (P < 0.001). The above results demonstrate that TRN mainly undertakes the task of information transmission in the auditory system. The noise response of TRN is more extensive than the tone response. Generally, TRN prefers high-intensity acoustic stimulation.
Rats ; Mice ; Animals ; Wakefulness ; Auditory Pathways/physiology* ; Rats, Wistar ; Mice, Inbred C57BL ; Thalamus/physiology*

OBJECTIVETo understand the influence of different sleep stages on respiratory regulation in normal people.

METHODSWe measured ventilation (VE) and occlusion pressure (P0.1) responses to hyperoxia hypercapnia (deltaVE/deltaPaCO2, deltaP0.1/deltaPaCO2) and isocapnic hypoxia (deltaVE/deltaSaO2 and deltaP0.1/deltaSaO2) in eleven non-snoring healthy people during wakefulness and during non-rapid eye movement (NREM) I + II, NREM III+IV, and rapid eye movement (REM) sleep stages.

RESULTSDuring NREM I + II and NREM III+IV, the normal subjects showed no significant decrease in P0.1, deltaP0.1/deltaSaO2 and deltaP0.1/deltaPaCO2 (P > 0.05), but deltaVE/ deltaSaO2 and deltaVE/ deltaPaCO2 decreased significantly (P < 0.05). During REM sleep, P0.1 maintained the level during wakefulness, but both hypoxic and hypercapnic responses decreased significantly (P < 0.05).

CONCLUSIONSSleep has significant influence on respiratory regulation in normal people. The respiratory drive (P0.1) in both NREM and REM sleep stages could maintain the awake level due to an effective compensation to the increase of upper airway resistance. The P0.1 responses to both hypoxia and hypercapnia decrease only in REM sleep stage, which is in consistent with the clinical phenomenon that sleep disordered breathing occurs in REM in normal people.

Adult ; Female ; Humans ; Hypercapnia ; physiopathology ; Hypoxia ; physiopathology ; Male ; Respiration ; Respiratory Physiological Phenomena ; Sleep Stages ; physiology ; Sleep, REM ; physiology ; Wakefulness ; physiology

Histaminergic neurons solely originate from the tuberomammillary nucleus (TMN) in the posterior hypothalamus and send widespread projections to the whole brain. Experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes. Endogeneous prostaglandin E2 and orexin activate histaminergic neurons in the TMN to release histamine and promote wakefulness. Conversely, prostaglandin D2 and adenosine inhibit histamine release by increasing GABA release in the TMN to induce sleep. This paper reviews the effects and mechanisms of action of the histaminergic system on sleep-wake regulation, and briefly discusses the possibility of developing novel sedative-hypnotics and wakefulness-promoting drugs related to the histaminergic system.
Adenosine ; physiology ; Animals ; Dinoprostone ; physiology ; Histamine ; metabolism ; physiology ; Hypothalamic Area, Lateral ; physiology ; Intracellular Signaling Peptides and Proteins ; physiology ; Neurons ; physiology ; Neuropeptides ; physiology ; Orexins ; Prostaglandin D2 ; physiology ; Sleep ; physiology ; Wakefulness ; physiology ; gamma-Aminobutyric Acid ; metabolism

gamma-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice.
Animals ; Anxiety ; Caffeine ; Central Nervous System ; gamma-Aminobutyric Acid* ; Mice* ; Motor Activity ; Neurotransmitter Agents ; Physiology ; Sleep Initiation and Maintenance Disorders ; Wakefulness

OBJECTIVETo observe the alterations of auditory brainstem response (ABR) in guinea pigs with gentamicin-induced hearing loss under awake and anesthetic conditions.

METHODSWe recorded the ABR in 20 normal guinea pigs and 20 with gentamicin-induced hearing loss before and after anesthesia for statistical analysis.

RESULTSNo significant difference was observed in the waveform, response threshold (RT), I and III peak latencies (PL), I-III interpeak latencies (IPL) of ABR between awake and anesthetic conditions in normal guinea pigs (P>0.05), nor did gentamicin-induced hearing loss showed obvious impact on the ABR parameters (P>0.05).

CONCLUSIONNo significant ABR alterations occur under awake and anesthetic conditions in either normal guinea pigs or those with hearing loss, therefore ABR test can be performed without anesthesia to ensure the success and error minimization of the experiment.

Anesthesia ; Animals ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Gentamicins ; Guinea Pigs ; Hearing Loss, Bilateral ; chemically induced ; physiopathology ; Random Allocation ; Wakefulness

Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Normal sleep comprises non-rapid eye movement (NREM) and REM periods that alternate through the night. Sleep usually begins in NREM and progresses through deeper NREM stages (2, 3, and 4 stages), but newborns enter REM sleep (active sleep) first before NREM (quiet sleep). A period of NREM and REM sleep cycle is approximately 90 minutes, but newborn have a shorter sleep cycle (50 minutes). As children mature, sleep changes as an adult pattern: shorter sleep duration, longer sleep cycles and less daytime sleep. REM sleep is approximately 50% of total sleep in newborn and dramatically decreases over the first 2 years into adulthood (20% to 25%). An initial predominant of slow wave sleep (stage 3 and 4) that peaks in early childhood, drops off abruptly after adolescence by 40% from preteen years, and then declines over the life span. The hypothalamus is recognized as a key area of brain involved in regulation of sleep and wakefulness. The basic function of sleep largely remains elusive, but it is clear that sleep plays an important role in the regulation of CNS and body physiologic processes. Understanding of the architecture of sleep and basic mechanisms that regulate sleep and wake cycle are essential to evaluate normal or abnormal development of sleep pattern changes with age. Reduction or disruption of sleep can have a significant impact on daytime functioning and development, including learning, growth, behavior, and emotional regulation.
Adolescent ; Adult ; Brain ; Child ; Eye Movements ; Humans ; Hypothalamus ; Infant, Newborn ; Learning ; Neurons ; Neurotransmitter Agents ; Physiology* ; Sleep, REM ; Wakefulness