The role of orexinergic system in the regulation of cataplexy.

Loss of orexin/hypocretin causes serious sleep disorder; narcolepsy. Cataplexy is the most striking symptom of narcolepsy, characterized by abrupt muscle paralysis induced by emotional stimuli, and has been considered pathological activation of REM sleep atonia system. Clinical treatments for cataplexy/narcolepsy and early pharmacological studies in narcoleptic dogs tell us about the involvement of monoaminergic and cholinergic systems in the control of cataplexy/narcolepsy.

Increase in Blood Pressure by Local Injection of Ketamine into the Amygdala in Rats.

To confirm that an increase in blood pressure induced by ketamine is mediated through the central nervous system, we examined the effect of ketamine, applied directly to the amygdala, on blood pressure. Six male Sprague-Dawley rats were used in the study. Under head-restrained and unanesthetized condition, 0.

[Comparison of Influence of Susceptibility Artifact due to Metallic Embolic Material in MRA Image].

Purpose: To identify the influence of susceptibility artifact caused by commonly used trans-catheter embolic devices for vascular lesions in the body on the images of various magnetic resonance angiography (MRA) techniques as an aid to patient screening after endovascular embolization.

Materials And Methods: We constructed vascular phantoms in which three embolic materials; platinum coil, Inconel coil, and vascular plug, were placed. Each phantom was imaged with three types of MRA techniques as follows: ultra-short echo time magnetic resonance imaging (UTE), three-dimensional fast advanced spin echo (3D-FASE), time-resolved contrast MRA with key hole technique (Key hole).

Assessment of the septal area neuronal activity during penile erections in rapid eye movement sleep and waking in the rats.

To understand the central mechanism of penile erections during rapid eye movement (REM) sleep and waking, single units were recorded from the septal area in un-anesthetized head-restrained rats simultaneous with erections. Erectile events were assessed by pressure in the bulb of the corpus spongiosum of the penis and bulbospongiosus-muscle activity. Of 143 recorded neurons, 36% showed increased activity (E-type) and 24% decreased activity (I-type) during different phases of erection in REM sleep, while 10% were E-type and 35% were I-type during erections in waking.

Sleep as a biological problem: an overview of frontiers in sleep research.

Sleep is a physiological process not only for the rest of the body but also for several brain functions such as mood, memory, and consciousness. Nevertheless, the nature and functions of sleep remain largely unknown due to its extremely complicated nature and lack of optimized technology for the experiments. Here we review the recent progress in the biology of the mammalian sleep, which covers a wide range of research areas: the basic knowledge about sleep, the physiology of cerebral cortex in sleeping animals, the detailed morphological features of thalamocortical networks, the mechanisms underlying fluctuating activity of autonomic nervous systems during rapid eye movement sleep, the cutting-edge technology of tissue clearing for visualization of the whole brain, the ketogenesis-mediated homeostatic regulation of sleep, and the forward genetic approach for identification of novel genes involved in sleep.

Chronic alterations in monoaminergic cells in the locus coeruleus in orexin neuron-ablated narcoleptic mice.

Narcolepsy patients often suffer from insomnia in addition to excessive daytime sleepiness. Narcoleptic animals also show behavioral instability characterized by frequent transitions between all vigilance states, exhibiting very short bouts of NREM sleep as well as wakefulness. The instability of wakefulness states in narcolepsy is thought to be due to deficiency of orexins, neuropeptides produced in the lateral hypothalamic neurons, which play a highly important role in maintaining wakefulness.

[Regulation of sleep and wakefulness through the monoaminergic and cholinergic systems].

Sleep and wakefulness are regulated in the brainstem and hypothalamus. Classical brain dissecting or stimulating studies have proposed the concept of an ascending reticular activating system, presently known as the wakefulness center, located in the caudal midbrain/rostral pontine (mesopontine) areas, comprising the serotonergic, noradrenergic and cholinergic neural populations. These neural groups, in association with the histaminergic and orexinergic neurons in the hypothalamus, activate the cerebral the cortex through the thalamus or basal forebrain.

Acupuncture of the sacral vertebrae suppresses bladder activity and bladder activity-related neurons in the brainstem micturition center.

Acupuncture of the sacral vertebrae has therapeutic effects in patients with overactive bladders. The mechanism of these effects, however, remains unclear. The present study, using urethane-anesthetized rats, investigated the effects of acupuncture stimulation of the sacral vertebrae on bladder activity and bladder activity-related neurons in and around Barrington's nucleus.

Role of the lateral preoptic area and the bed nucleus of stria terminalis in the regulation of penile erection.

To elucidate the role of the preoptic area (POA) in the regulation of penile erection, we examined the effects of electrical stimulation in and around the POA on penile erection in rats, which was assessed by changes in pressure in the corpus spongiosum of the penis (CSP) and electromyography (EMG) of the bulbospongiosus (BS) muscle. In unanesthetized and anesthetized rats, four types of responses were induced by stimulation in and around the POA; (1) normal type responses, which were similar to spontaneously occurring erections, characterized by slow increase in CSP pressure and sharp peaks concurrent with BS muscle bursting; (2) muscular type responses, which included sharp CSP pressure peaks (muscular component) with almost no vascular component; (3) mixed type responses, which included a sequence of high-frequency CSP peaks followed by low-frequency CSP peaks; and (4) micturition type responses, which had higher-frequency and lower-amplitude CSP peaks than other responses which were identical to those of normal micturition. In unanesthetized condition, erections were evoked by stimulation of the lateral preoptic area (LPOA), medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN), reuniens thalamic nucleus (Re) and lateral septum (LS).

Penile erection and micturition events triggered by electrical stimulation of the mesopontine tegmental area.

The cholinergic neurons in the laterodorsal tegmental nucleus (LDT) play a crucial role in the regulation of rapid eye movement (REM) sleep. Because penile erection occurs during REM sleep, the involvement of the LDT in penile erection was examined in unanesthetized head-restrained rats. To detect penile erection, corpus spongiosum of the penis (CSP) pressure was measured through a telemetric device with simultaneous bulbospongiosum (BS) muscle EMG recording through stainless wires.

Suppressive effect of acupuncture stimulation to the sacral segment on the state of vigilance and the brainstem cholinergic neurons.

The effects of acupuncture stimulation to the sacral segment on the electroencephalogram (EEG) and activity of the cholinergic neurons in the laterodorsal tegmental nucleus (LDT) were examined in urethane-anesthetized rats. When EEG was small amplitude and higher frequency, the stimulation to the sacral segment induced large amplitude and slow EEG with latencies ranged from 45 sec to 12 min, and durations from 48 sec to 56 min. The stimulus induced EEG is composed of significant increase in delta power and significant decrease in theta and beta powers.

Acupuncture stimulation to the sacral segment affects state of vigilance in rats.

The effects of acupuncture stimulation to the sacral segment on electroencephalograms (EEGs) and activity of locus coeruleus (LC) neurons were examined in urethane-anesthetized rats. In 71 of 112 trials, when EEGs displayed small amplitude and high frequency, stimulation to the sacral segment-induced large amplitude and slow EEGs with a latency of <450s and duration ranged from 32s to >42 min. Stimulus-induced EEGs comprised significant increases in delta power and significant decreases in theta and beta powers.

Requirement of tryptophan hydroxylase during development for maturation of sensorimotor gating.

Deficits in sensorimotor gating, a function to focus on the most salient stimulus, could lead to a breakdown of cognitive integrity, and could reflect the "flooding" by sensory overload and cognitive fragmentation seen in schizophrenia. Sensorimotor gating emerges at infancy, and matures during childhood. The mechanisms that underlie its development are largely unclear.

Postnatal development of cholinergic neurons in the mesopontine tegmentum revealed by histochemistry.

Cholinergic neurons in the laterodorsal tegmental nucleus (LDT) and pedunculopontine tegmental nucleus (PPT) play a role in the regulation of several kinds of behavior. Some of them, such as locomotion, motor inhibition or sleep, show dramatic changes at a certain period of postnatal development. To understand the neural substrate for the development of these physiological functions, we studied the development of cholinergic neurons in the LDT and PPT of postnatal and adult rats using histochemical staining of NADPH-diaphorase (NADPH-d) and immunohistochemical staining of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT).

A quartet neural system model orchestrating sleep and wakefulness mechanisms.

Physiological knowledge of the neural mechanisms regulating sleep and wakefulness has been advanced by the recent findings concerning sleep/wakefulness-related preoptic/anterior hypothalamic and perifornical (orexin-containing)/posterior hypothalamic neurons. In this paper, we propose a mathematical model of the mechanisms orchestrating a quartet neural system of sleep and wakefulness composed of the following: 1) sleep-active preoptic/anterior hypothalamic neurons (N-R group); 2) wake-active hypothalamic and brain stem neurons exhibiting the highest rate of discharge during wakefulness and the lowest rate of discharge during paradoxical or rapid eye movement (REM) sleep (WA group); 3) brain stem neurons exhibiting the highest rate of discharge during REM sleep (REM group); and 4) basal forebrain, hypothalamic, and brain stem neurons exhibiting a higher rate of discharge during both wakefulness and REM sleep than during nonrapid eye movement (NREM) sleep (W-R group). The WA neurons have mutual inhibitory couplings with the REM and N-R neurons.

Orexinergic projections to the cat midbrain mediate alternation of emotional behavioural states from locomotion to cataplexy.

Orexinergic neurones in the perifornical lateral hypothalamus project to structures of the midbrain, including the substantia nigra and the mesopontine tegmentum. These areas contain the mesencephalic locomotor region (MLR), and the pedunculopontine and laterodorsal tegmental nuclei (PPN/LDT), which regulate atonia during rapid eye movement (REM) sleep. Deficiencies of the orexinergic system result in narcolepsy, suggesting that these projections are concerned with switching between locomotor movements and muscular atonia.

Subthalamic neurons coordinate basal ganglia function through differential neural pathways.

The subthalamic nucleus (STN) is a key component of basal ganglia circuitry that mediates a variety of motor functions. The STN neurons send glutamatergic projections to the output structures of basal ganglia, including the substantia nigra pars reticulata (SNr) and the entopeduncular nucleus, and also innervate the globus pallidus (GP). However, the mechanism by which the STN regulates motor functions in the neural circuitry is not fully understood.

Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice.

The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic method to map upstream neuronal populations that have synaptic connections to orexin neurons and revealed that orexin neurons receive input from several brain areas.

State-dependent effects of orexins on the serotonergic dorsal raphe neurons in the rat.

The serotonergic dorsal raphe (DR) neurons play an important role in sleep-wakefulness regulation. Orexinergic neurons in the lateral hypothalamus densely project to the brainstem sites including the DR. To test the effects of orexins on the serotonergic DR neurons, we applied orexin A (0.

The orexinergic synaptic innervation of serotonin- and orexin 1-receptor-containing neurons in the dorsal raphe nucleus.

Orexin/hypocretin has been well demonstrated to excite the serotonergic neurons in the dorsal raphe nucleus (DRN). We studied the morphological relationships between orexin-containing axon terminals and serotonin- as well as orexin-receptor-containing neurons in the dorsal raphe nucleus. Using immunohistochemical techniques at the light microscopic level, orexin A (OXA)-like immunoreactive neuronal fibers in the DRN were found to make close contact with serotonergic neurons, while some of the serotonergic neurons also expressed the orexin 1 receptor (OX1R).

Modulation by desmopressin of neuronal activity in brainstem micturition center.

Objectives: To examine the effect of desmopressin (DDAVP) on bladder contraction and on the neurons that fire in relation to spontaneous bladder contraction (bladder-related neurons) in and around Barrington's nucleus, the micturition center. DDAVP is used for the treatment of nocturnal enuresis because of its antidiuretic action, but the mechanism of this action has not been proved.

Methods: Urethane-anesthetized Sprague-Dawley male rats (n = 20) were used.

Is state-dependent alternation of slow dynamics in central single neurons during sleep present in the rat ventroposterior thalamic nucleus?

Based upon our previous results in cats, we hypothesized that neurons in the central processor systems of the brain generally exhibit state-dependent dynamics alternation of slow fluctuations in spontaneous activity during sleep. To test the validity of this hypothesis across species, we recorded single neuronal activity during sleep from the ventroposterior (VP) thalamic nucleus in unanesthetized, head-restrained rats. Spectral analysis was performed on successive spike-counts of neuronal activity recorded during three stages of the sleep-wakefulness cycle: wakefulness (W, n=6), slow-wave sleep (SWS, n=20), and paradoxical sleep (PS, n=32).

Firing of micturition center neurons in the rat mesopontine tegmentum during urinary bladder contraction.

Micturition is controlled by a network of brainstem neurons involving the Barrington's nucleus. To depict clearly the brainstem system for micturition control, the present study was designed to record single neuronal activity in the mesopontine tegmentum including the Barrington's nucleus, and to observe its precise timing in relation to bladder contraction recorded simultaneously. About 1/5 of neurons encountered had firing modulated in relation to bladder contraction.

Firing properties of neurones in the laterodorsal hypothalamic area during sleep and wakefulness.

In undrugged, head-restrained rats, neuronal activity was recorded in and around the laterodorsal hypothalamic area where orexin neurones are distributed. Among 22 neurones observed across whole sleep-waking states, half (n = 11) were most active during paradoxical sleep and least active during waking. Others were equally more active during paradoxical sleep and waking than during slow-wave sleep (n = 6), or were most active during waking and least active during paradoxical sleep (n = 3).

Effects of orexin on the laterodorsal tegmental neurones.

Orexin, a hypothalamic neuropeptide, has been revealed to be involved in sleep regulation. To elucidate functions of orexin in brainstem sleep regulation mechanism, we examined the effects of orexin applied from micropipettes with air pressure on neurones in and around the laterodorsal tegmental nucleus (LDT). In five of seven cholinergic neurones and six of nine non-cholinergic neurones orexin induced long-lasting excitation.