Biomedical subjects

Yoshimasa Koyama

Publications and source records attributed to Yoshimasa Koyama.

14 recordsLinked to original sources

PubMed2006

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. Here, we screened the mouse genome, and found that tryptophan hydroxylase (TPH) is implicated in the maturation of sensorimotor gating. TPH, an enzyme involved in the biosynthesis of serotonin, proved to be required only during the weaning period for maturation of sensorimotor gating, but was dispensable for its emergence. Proper serotonin levels during development underlie the mature functional architecture for sensorimotor gating via appropriate actin polymerization. Thus, maintaining proper serotonin levels during childhood may be important for mature sensorimotor gating in adulthood.

Acoustic Stimulation↗

PubMed2005

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). At postnatal day 1 (P1), ChAT- and VAChT-stained cells localized more dorsally than those of NADPH-d-stained cells, and at P7 their distributions became similar to those of NADPH-d-stained cells. The number of NADPH-d-stained cells increased rapidly after birth, reaching the adult level by P7. In contrast, the number of ChAT- and VAChT-stained cells and the intensity of their staining decreased from P1 to P3 and then increased through P21. The volume of the LDT increased during the second postnatal week. These findings indicate that cholinergic neurons in the LDT develop their cholinergic properties during the second postnatal week and mature functionally thereafter. We discuss these results in light of the several physiological functions regulated by the cholinergic neurons in the mesopontine tegmentum.

Age Factors↗

PubMed2005

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. The W-R neurons have mutual excitatory couplings with the WA and REM neurons. The REM neurons receive unidirectional inhibition from the N-R neurons. In addition, the N-R neurons are activated by two types of sleep-promoting substances (SPS), which play different roles in the homeostatic regulation of sleep and wakefulness. The model well reproduces the actual sleep and wakefulness patterns of rats in addition to the sleep-related neuronal activities across state transitions. In addition, human sleep-wakefulness rhythms can be simulated by manipulating only a few model parameters: inhibitions from the N-R neurons to the REM and WA neurons are enhanced, and circadian regulation of the N-R and WA neurons is exaggerated. Our model could provide a novel framework for the quantitative understanding of the mechanisms regulating sleep and wakefulness.

Adenosine↗

PubMed2005

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. The present study characterizes the role of these orexinergic projections to the midbrain. In decerebrate cats, injecting orexin-A (60 microm to 1.0 mm, 0.20-0.25 microl) into the MLR reduced the intensity of the electrical stimulation required to induce locomotion on a treadmill (4 cats) or even elicit locomotor movements without electrical stimulation (2 cats). On the other hand, when orexin was injected into either the PPN (8 cats) or the substantia nigra pars reticulata (SNr, 4 cats), an increased stimulus intensity at the PPN was required to induce muscle atonia. The effects of orexin on the PPN and the SNr were reversed by subsequently injecting bicuculline (5 mm, 0.20-0.25 microl), a GABA(A) receptor antagonist, into the PPN. These findings indicate that excitatory orexinergic drive could maintain a higher level of locomotor activity by increasing the excitability of neurones in the MLR, while enhancing GABAergic effects on presumably cholinergic PPN neurones, to suppress muscle atonia. We conclude that orexinergic projections from the hypothalamus to the midbrain play an important role in regulating motor behaviour and controlling postural muscle tone and locomotor movements when awake and during sleep. Furthermore, as the excitability is attenuated in the absence of orexin, signals to the midbrain may induce locomotor behaviour when the orexinergic system functions normally but elicit atonia or narcolepsy when the orexinergic function is disturbed.

Animals↗

PubMed2005

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. Here we performed conditional ablation of the STN neurons by using immunotoxin-mediated cell targeting. We then analyzed dopamine (DA)-mediated motor behavior and firing activity of the SNr and GP neurons. Ablation of the STN neurons increased spontaneous movement and reduced hyperactivity in response to DA stimulation. Ablation of these neurons modulated the pattern and rate of spontaneous firing of the SNr neurons, although it did not substantially affect spontaneous firing of the GP neurons. The ablation attenuated DA-induced suppression of the firing rate of the SNr neurons and inhibited DA-induced elevation of the rate of the GP neurons. In addition, pharmacological blockade of GP activation in response to DA stimulation inhibited the suppression of SNr activity and the resultant motor activation. These results suggest that the STN neurons suppress spontaneous behavior through their direct projection to the output neurons and that, in response to DA, they contribute to expression of behavior by acting on the output neurons mainly through the GP-mediated pathways. We conclude that the STN coordinates motor behavior through differential neural pathways depending on the state of DA transmission.

Action Potentials↗

PubMed2005

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. These include the amygdala, basal forebrain cholinergic neurons, GABAergic neurons in the preoptic area, and serotonergic neurons in the median/paramedian raphe nuclei. Monoamine-containing groups that are innervated by orexin neurons do not receive reciprocal connections, while cholinergic neurons in the basal forebrain have reciprocal connections, which might be important for consolidating wakefulness. Electrophysiological study showed that carbachol excites almost one-third of orexin neurons and inhibits a small population of orexin neurons. These neuroanatomical findings provide important insights into the neural pathways that regulate sleep/wakefulness states.

Animals↗

PubMed2005

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 (0.1 mM) by pressure to these neurons in unanesthetized and urethane anesthetized rats. Orexin A caused excitation in 10 of 15 neurons under unanesthetized condition. The excitation was characterized by slow onset (0-18 s), long lasting duration (15-150 s) and state-dependency. Orexin A applied during REM sleep or slow wave sleep induced significant excitation while during wakefulness, the similar amount of orexin A did not increase the firing rate any more. In the anesthetized animals, orexin A induced excitation in four of eight neurons. The excitation had slow onset and was long lasting. These results suggest that orexinergic neurons exert excitatory influence on the serotonergic DR neurons to maintain tonic activity of them, thereby participating in regulation of sleep-wakefulness cycles and other functions.

Animals↗

PubMed2005

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). At the electron microscopic level, double-immunostaining experiments showed that the orexin A-like immunoreactive fibers were present mostly as axon terminals that made synapses on the serotonin- and orexin 1-receptor-containing neurons. While only axodendritic synapses between orexin A-containing axon terminals and serotonergic neurons were detected, the synapses made by orexin A-containing axon terminals on the orexin 1-receptor-containing neurons were both axodendritic and axosomatic. The present study suggests that excitation effect of orexin A on dorsal raphe serotonergic neurons is via synaptic communication through orexin 1 receptor.

Animals↗

PubMed2004

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). We found that firing of VP neurons displayed white-noise-like dynamics over the range of 0.04-1.0 Hz during SWS and 1/f-noise-like dynamics over the same range during PS. We also demonstrated for the first time that the slow dynamics of neuronal activity during quiet wakefulness (but not drowsiness) are white-noise-like. These results suggest that our hypothesis is true across species. During W and SWS, the brain may be considered as under global inhibition. Conversely, PS may represent a state of global disinhibition in the brain, where neuronal activity exhibits 1/f-noise-like dynamics. Fluctuations observed in living organisms may be involved in essential processes in generation and function of sleep states.

Action Potentials↗

PubMed2004

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. DDAVP was infused intravenously or as an intracerebroventricular infusion into the lateral ventricle. RESULTS: We encountered three types of bladder-related neurons: those that fired before the start of the contraction (type E1), those that fired synchronous with the bladder contraction (type E2), and those that fired during bladder relaxation (type I). Intravenous infusion caused inhibition in three of five type E1 neurons, excitation in two of five type E2 neurons, and excitation (one neuron) and inhibition (one neuron) of four type I neurons. With intracerebroventricular infusion into the lateral ventricle, two of four type E1 neurons were inhibited, and one of seven type E2 neurons and three of four type I neurons were excited. Bladder contraction was suppressed in 4 of 12 rats by intravenous infusion and in 2 of 8 rats by intracerebroventricular infusion into the lateral ventricle. In all cases, when the bladder contraction was suppressed, an electroencephalogram of larger amplitude and slower frequency appeared. CONCLUSIONS: DDAVP seems to regulate bladder activity by affecting bladder-related neurons in the micturition center.

Animals↗

PubMed2003

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. Three types of neurons were distinguished; those which fired only prior to the start of contraction (type E1), those whose firing started shortly prior to and was maintained during contraction (type E2), and those whose firing was strongly suppressed during contraction (type I). Type E2 neurons were most frequently observed in the Barrington's nucleus and its close vicinity, while the neurons of the other two types were scattered widely in the mesopontine tegmentum. The results show clearly that direct neural signals to induce bladder contraction may arise from the Barrington's nucleus, and that the nucleus may receive regulatory inputs from wide areas of the mesopontine tegmentum. In addition, the present study clarified that the noradrenergic and cholinergic neurons, which are located in nuclei adjoining the Barrington's nucleus and function to control sleep/wakefulness, may not be concerned in controlling micturition directly.

Action Potentials↗

PubMed2002

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. These results suggest that hypothalamic orexin neurones may affect the LDT neurones directly, and thereby participate in control of sleep.

Animals↗

PubMed2002

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). The majority of neurones started to increase firing activity prior to the transition of sleep-waking states. These results suggest that the area of the hypothalamus containing orexin neurones plays a role in sleep-waking regulation.

Action Potentials↗

PubMed2002

Effects of acupuncture to the sacral segment on the bladder activity and electroencephalogram.

Using urethane-anaesthetized rats, the effects of acupunctural stimulation to the sacral segment on the urinary bladder activity and cortical electroencephalogram (EEG) were examined. The acupuncture suppressed urinary bladder activity in 36 of 68 trials. On many occasions (22/36 trials), suppression was accompanied by an increase in EEG amplitude. In such cases, the EEG power increased in all frequency bands after stimulation. The same EEG changes could be induced when the bladder was empty with no contraction. The results suggest that acupuncture stimulation affects both the bladder activity and sleep-arousal system.

Acupuncture↗