Ichiro Kita

Generation of hiccup by electrical stimulation in medulla of cats

The present study has revealed that a hiccup-like response (a brief powerful inspiratory activity accompanied by glottic adduction) can be generated by electrical stimulation to a limited area within the medullary reticular formation of the cat. This finding indicates that there is a neuronal network coordinating the hiccup reflex within the lower brain stem.

Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat

Orexin-A is a neuropeptide which has been suggested to be involved in sleep and arousal mechanisms. Orexin-A, for example, stimulates arousal when administrated intracerebroventricularly to rats. We attempted to identify specific neural sites of orexin-A and orexin-B action. Orexin-A and orexin-B were microinjected into the medial parvocellular subdivision of the paraventricular nucleus (PVN) in anesthetized, spontaneously breathing rats, and cortical arousal and yawning responses were assessed. Cortical arousal responses were monitored with the electrocorticogram (ECoG), and yawning responses were evaluated by monitoring intercostal electromyograms as an index of inspiratory activity and digastric electromyograms as an indicator of mouth opening. We also measured blood pressure and heart rate during yawning responses, since yawning is accompanied by changes in autonomic activity. Microinjection of orexin-A into the PVN elicited an arousal shift in the ECoG to lower voltage and faster rhythms. This cortical arousal response was followed by a single large inspiration with mouth opening, i.e. a yawning response. On the other hand, microinjection of orexin-B into the PVN elicited an arousal shift in the ECoG without yawning responses. These results demonstrate that an orexin receptive site for triggering arousal/yawning responses exists in the PVN, and suggest that the PVN is involved in arousal mechanisms.

Yawning responses induced by local hypoxia in the paraventricular nucleus of the rat.

Yawing was induced by microinjections of L-glutamate, cyanide and a nitric oxide-releasing compound (NOC12) into the paraventricular nucleus of the hypothalamus (PVN) in anesthetized, spontaneously breathing rats. To evaluate physiological aspects of yawning, we monitored intercostal electromyogram (EMG) as an index of inspiratory activity, digastric EMG, blood pressure and electrocorticogram (ECoG). Microinjection of L-glutamate in the medial parvocellular subdivision (mp) elicited a stereotyped yawning response, i.e. an initial depressor response and an arousal shift in ECoG followed by a single large inspiration with mouth opening. The same sequential events were observed during spontaneous yawning, indicating that the mp is responsible for triggering yawning. Microinjection of cyanide into the mp caused the same yawning responses as the ones elicited by microinjection of L-glutamate, suggesting that the mp is sensitive to chemical hypoxia or ischemia within the PVN. Microinjection of NOC12 into the mp elicited a single large inspiration with a variable onset delay, suggesting that diffusible nitric oxide (NO) within the mp may act as a paracrine agent to cause a yawning response. We hypothesize that the mp of the PVN contains an oxygen sensor that causes a yawning response.

Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats.

Our previous studies have suggested that activation of the hypothalamic paraventricular (PVN) descending oxytocinergic projections is involved in the induction of yawning accompanied by an arousal response, but the possibility that neural systems other than the oxytocinergic system in the PVN also mediate the arousal/yawning response cannot be ruled out. We assessed the activity of corticotropin-releasing factor (CRF) neurons during yawning induced by the PVN stimulation in anesthetized, spontaneously breathing rats using double-staining for c-Fos and CRF. Yawning response was evaluated by monitoring an intercostals electromyogram as an index of inspiratory activity and a digastric electromyogram as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG) to determine the arousal response during yawning. Microinjection of l-glutamate (2-5 nmol) into the PVN produced a frequent yawning accompanied by an arousal shift in the ECoG, and these behavioral effects were associated with a significant increase of c-Fos positive CRF neurons in the medial parvocellular subdivision of the PVN. In addition, a marked enhancement in the c-Fos expression was found in the both locus coeruleus (LC) and global area in the cortex when the frequency of yawning response was increased by the PVN stimulation, suggesting that the arousal response during yawning might be mediated by the activation of LC neurons. The present study suggests that an activation of CRF neurons in the PVN is responsible for the arousal response accompanied by yawning behavior.

Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat

The effects of microinjection of histamine into the paraventricular nucleus (PVN) of the hypothalamus on yawning responses were investigated in anesthetized, spontaneously breathing rats. Yawning responses were evaluated by monitoring the intercostal electromyogram (EMG) as an index of inspiratory activity and digastric EMG as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG) to determine the arousal response during yawning. Autonomic function was evaluated by measuring blood pressure and heart rate. Microinjection of histamine into the medial parvocellular subdivision (mp) of the PVN elicited a yawning response, i.e. a single large inspiration with mouth opening, and an arousal shift in ECoG to lower voltage and faster rhythms. Microinjection of HTMT dimaleate, an H1 receptor agonist, into the PVN also caused the yawning/arousal response. Pretreatment with pyrilamine, an H1 receptor antagonist, inhibited the histamine induced yawning behavior. These data demonstrate that a histamine receptive site for triggering yawning/arousal responses exists in the PVN, and suggest that these responses are mediated by activation of H1 receptor within the PVN.

Light induces cortical activation and yawning in rats.

We examined the effects of light stimulation on cortical activation and yawning response in anesthetized, spontaneously breathing rats. Cortical activation was assessed by means of an electrocorticogram (ECoG) and yawning response was evaluated by monitoring an intercostal electromyogram as an index of inspiratory activity and a digastric electromyogram as an indicator of mouth opening. Light stimulation elicited an arousal shift in the ECoG to faster rhythms. This arousal response was followed by a single large inspiration with mouth opening, i.e. a yawning response. Higher light intensity significantly reduced the onset latency of the arousal/yawning response. Pretreatment with pyrilamine, an H1-histamine receptor antagonist, injected into the lateral ventricle blocked both the cortical activation and the yawning response induced by light stimulation, suggesting a role of brain histaminergic neurotransmission in modulating the light-induced arousal/yawning responses.

Two Distinct Descending Inputs to the Cricothyroid Motoneuron in the Medulla Originating from the Amygdala and the Lateral Hypothalamic Area

1. The retrograde labelling study revealed that there are at least two independent descending pathways from the limbic system to the ventral medulla, i.e., the hypothalamo-medullary pathway and the amygdalo-medullary pathway. 2. The stimulation in the lateral hypothalamic area produced parasympathetic excitation and vocalization response: the recruited motor unit of CT muscle occurred in the late expiratory phase. By contrast, the stimulation at the medial part of the amygdala evoked sympathetic excitation and expiratory braking: the recruited motor unit of CT muscle occurred in the early expiratory phase or in the post-in-spiratory phase. 3. The present physiological study provided further important information on dual innervation of the cricothyroid muscle of the larynx: one motor unit with inspiratory firing is generated in the medulla, whereas the other motor unit with expiratory firing is evoked by a descending input from the limbic system.

Adrenergic cell group in rostral ventrolateral medulla of cat: its correlation with central chemoreceptors

We have proposed a hypothesis that secondary neurons mediating central respiratory chemoreception are not restricted to the medullary superficial layer. This idea was further examined in the present physiological and morphological studies. We identified the S area, i.e. the medullary surface area where cold blockade produced apnea, in anesthetized, spontaneously breathing cat. We then evaluated how the apnea was modified by injection of CO2-saturated saline into the vertebral-basilar artery. The CO2 injection caused immediate reappearance of respiratory rhythm, although intensity of inspiratory activity was smaller than in the control. This incomplete recovery suggests that the responsive structure extends deeply below the surface. The extent of the cell group underlying the S area was evaluated by morphological study. Medullary transverse sections including the S area were treated with three distinct antisera against phenylethanolamine N-methyltransferase (PNMT), dopamine-beta-hydroxylase (DBH), and 5-hydroxytryptamine (5-HT). The PNMT-labelled cell group was found to exactly underlie the S area, although the DBH- and the 5-HT-labelled cell groups did not show close topographic correlation with the S area. PNMT cells were located in the region ventral to retrofacial nucleus within 0.5-1.5 mm depth beneath the surface. These results suggest that adrenergic cells in the rostral ventrolateral medulla are important candidates for secondary neurons mediating central respiratory chemoreception.

Effects of practice on cardiorespiratory responses during postural control.

The present study examined the effects of practice of a balance test on cardiorespiratory changes in response to a 1-min balance test performed by standing on one leg with eyes closed (SOLEC) in 30 females (n=15, 21±4 years, mean±SD, for the experimental group; n=15, 22±4 years for the control group). Blood pressure (BP), heart rate (HR), minute ventilation (VE), respiratory rate (RR), tidal volume (VT), expiratory duration (Te), inspiratory duration (Ti), and oxygen uptake (VO2) were measured during the balance test before and after 2xa0wk of daily practice. The experimental group was given a daily 15-min practice session for the balance test. In contrast, the control group was instructed not to do any special practice for the balance test. In both the experimental and control groups, SOLEC induced significant increases in BP, HR, VE, RR, and VO2, and decreases in Te and Ti. Following the practice sessions, the balance time increased significantly in the experimental group (P<0.01). In addition, 2xa0wk of practice reduced the increases in BP (P<0.01), VE (P<0.05), and RR (P<0.01), and prolonged Te (P<0.01) during the SOLEC test. These results suggest that practice of a postural task affects cardiorespiratory responses to the balance test in addition to postural control.