Le bâillement, du réflexe à la pathologie
Le bâillement : de l'éthologie à la médecine clinique
Le bâillement : phylogenèse, éthologie, nosogénie
 Le bâillement : un comportement universel
La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
 
Fetal yawning assessed by 3D and 4D sonography
Le bâillement foetal
Le bâillement, du réflexe à la pathologie
Le bâillement : de l'éthologie à la médecine clinique
Le bâillement : phylogenèse, éthologie, nosogénie
 Le bâillement : un comportement universel
La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
 
Fetal yawning assessed by 3D and 4D sonography
Le bâillement foetal
http://www.baillement.com

mystery of yawning 

 

 

 

 

mise à jour du
21 juillet 2019
Behavioural Brain Research
2019;371:111974
Central nucleus of the amygdala is involved
in induction of yawning response in rats
 
Natsuko Kubota, Seiichiro Amemiya, Shinya Yanagita,
Takeshi Nishijima, Ichiro Kita
Department of Human Health Science, Tokyo Metropolitan University, Japan

Chat-logomini

-Kita I, Kubota N, Yanagita S, Motoki C Intracerebroventricular administration of corticotropin-releasing factor antagonist attenuates arousal response accompanied by yawning behavior in rats. Neurosci.Letter 2008;433(3):205-208 
-Kita I, Yoshida Y, Nishino S. An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection. Neurosci Res. 2006;54(4):269-275
-Kita I, Seki Y, Nakatani Y, Fumoto M, Oguri M, Sato-Suzuki I, Arita H. Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats. Behav Brain Res. 2006;169(1)48-56.
-Kita I, Sato-Suzuki et al.Yawning responses induced by local hypoxia in the paraventricular nucleus of the rat.Behavioural Brain Research 2000;117(1-2):119-126
-Kubota N, Amemiya S, Motoki C, Otsuka T, Nishijima T, Kita I. Corticotropin-releasing factor antagonist reduces activation of noradrenalin and serotonin neurons in the locus coeruleus and dorsal raphe in the arousal response accompanied by yawning behavior in rats. Neurosci Res. 2012;72(4):316-323
-Kubota N, Amemiya S, Yanagita S, Nishijima T, Kita I. Emotional stress evoked by classical fear conditioning induces yawning behavior in rats. Neurosci Lett. 2014;566:182-187
-Sato-Suzuki I, Kita I, Oguri M, Arita H Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat Journal of Neurophysiology, 1998;80(5)2765-2775
-Sato-Suzuki I, I Kita, Seki Y, M Oguri, H Arita Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat Behavioural Brain Research 2002;128:169-177
-Seki Y, Y Nakatani, et al Light induces cortical activation and yawning in rat Behav Brain Res 2003;140(1-2):65-73
-Seki Y, Sato-Suzuki I, et al Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat. Behav Brain Res. 2002;134(1-2):75-82.

Yawning behavior is characterized by mouth opening accompanied by deep inspiration, as well as arousal response, and is often observed not only in states of boredom or drowsiness, but also in stressful emotional situations in humans and animals. These phenomena suggest that yawning response may be an emotional behavior, possibly through activation of the central nucleus of amygdala (CeA), which is a critical region for emotional responses.
 
However, the involvement of the CeA in triggering yawning remains unknown. Here, we investigated whether neuronal activation of the CeA by microinjection of L-glutamate into the CeA is able to induce stereotyped yawning responses in anesthetized, spontaneously breathing rats. In addition, we assessed the effects of the CeA stimulation on the activation of oxytocin (OT) and CRF (corticotropin-releasing factor) neurons in the paraventricular nucleus of the hypothalamus (PVN), which is responsible for induction of yawning, using c-Fos immunohistochemistry. Microinjection of L-glutamate into the CeA causes an initial depressor response in the blood pressure and an arousal shift on the electrocorticogram followed by a single inspiration, which is the same as the typical pattern of the stereotyped yawning response induced by the PVN stimulation. In addition, the CeA stimulation activated the neuronal activities of both OT and CRF neurons in the PVN, as well as yawning responses.
 
These results indicate that activation of the CeA is involved in the induction of yawning response, suggesting that yawning is an emotional behavior.

  
Le bâillement se caractérise par une large ouverture de la bouche accompagnée d'une inspiration profonde et par une stimulation de la vigilance. On l'observe souvent non seulement dans des états d'ennui ou de somnolence, mais également dans des situations émotionnelles stressantes chez l'homme et les animaux. Ces phénomènes suggèrent que le bâillement peut être un comportement émotionnel, possiblement par l'activation du noyau central de l'amygdale (CeA), une région critique pour les réponses émotionnelles. Cependant, l'implication de la CeA dans le déclenchement du bâillement reste inconnue.
 
Ici, les auteurs ont examiné si l'activation neuronale du CeA par microinjection de L-glutamate dans le CeA est capable d'induire des bâillements stéréotypés chez des rats anesthésiés et respirant spontanément. De plus, ils ont évalué les effets de la stimulation du CeA sur l'activation des neurones ocytocinocynergiques (OT) et CRF (facteur de libération de la corticotropine) dans le noyau paraventriculaire de l'hypothalamus (PVN), responsable de l'induction du bâillement, à l'aide de Immunohistochimie de Fos. La microinjection de L-glutamate dans la CeA provoque une réponse dépressive initiale de la pression artérielle et un décalage de l'excitation sur l'électrocorticogramme, suivis d'une seule inspiration, ce qui correspond au schéma typique d'un bâillement stéréotypée induite par la stimulation PVN. En outre, la stimulation su CeA a activé les activités neuronales des neurones OT et CRF dans le PVN, ainsi que des bâillements. Ces résultats indiquent que l'activation du CeA est impliquée dans l'induction du bâillement, suggérant que bâiller est un comportement émotionnel.

1. Introduction
Yawning behavior is primarily characterized by mouth opening accompanied by deep inspiration, stretching of the trunk, and autonomic responses, as well as arousal response. Many studies have indicated that the paraventricular nucleus of the hypothalamus (PVN) is critical for the occurrence of yawning behavior [2,27]. Indeed, our previous studies have demonstrated that electrical and/or chemical stimulation of the PVN can evoke a stereotyped yawning response, i.e., an initial depressor response and an arousal shift on electrocorticogram (ECoG) followed by a single large inspiration with mouth opening, in anesthetized, spontaneously breathing rats [17,35]. In addition, we have reported that an increase in the frequency of spontaneous yawns accompanied by an arousal shift on ECoG was observed after micro-injections of L-glutamate into the PVN [18,35]. Furthermore, it has been indicated that activation of oxytocin (OT) and corticotropin-releasing factor (CRF) neurons in the PVN, each of which sends descending axons to the lower brainstem involved in either arousal, respiratory, cardiovascular, or other autonomic functions, mediates the induction of yawning accompanied by arousal response [1,2,18&endash;20]. Recently, we reported that emotional stress evoked by classical fear conditioning induces yawning behavior accompanied by activation of both OT and CRF neurons in the PVN, as well as the central nucleus of the amygdala (CeA) in freely moving rats [21]. The CeA, which is part of the amygdaloid complex, is known to be essential for the expression of emotional responses, including behavioral, autonomic and hormonal responses during stressful situations [23,25]. Furthermore, neuroanatomical studies have shown that the CeA directly innervates parvocellular regions in the PVN, which contains OT and CRF neurons [6,13,15]. Therefore, it is possible that activation of the CeA may mediate the induction of yawning behavior via activation of OT and CRF neurons in the PVN. However, the involvement of the CeA in triggering yawning remains unknown.
 
In the present study, we investigated whether neuronal activation in the CeA by microinjection of L-glutamate into the CeA induces stereo- typed yawning responses in anesthetized, spontaneously breathing rats, and compared those responses with stereotyped yawning responses by microinjection of L-glutamate into the PVN. In addition, we assessed L-glutamate into the CeA (about 10 times for 60 min) to evaluate frequency of spontaneous yawns as repeated stimuli-response and activity of OT and CRF neurons in the PVN during yawning responses using c- Fos immunohistochemistry.
 
2.4. Determination of yawning response
We determined yawning response according to our previous studies [15,28]. Briefly, we defined a typical response pattern characterized by an initial depressor response and an arousal shift in ECoG followed by a single large inspiration in anesthetized and spontaneously breathing rats as a yawning response. In experimental observation, the latency of a single large inspiration from the onset of microinjection of L-glutamate into either the CeA or PVN was measured. In addition, we counted the number of both yawning responses and microinjections, and calculated the occurrence rate of yawning responses induced by micro-injection of L-glutamate into either the CeA or PVN (number of induced yawning/number of microinjections).
 
4. Discussion
The present study physiologically demonstrated that neuronal activation of the CeA could induce stereotyped yawning responses. Microinjection of L-glutamate into the CeA caused an initial depressor response and an arousal shift on the ECoG followed by a single large inspiration in anesthetized, spontaneously breathing rats. This response pattern was almost the same as the typical pattern of stereotyped yawning response induced by the PVN stimulation. In addition, siginificant increases in neuronal activities of both OT and CRF neurons in the PVN were observed during the yawning responses induced by chemical stimulation of the CeA. Therefore, this study suggests that the CeA has the potential to induce stereotyped yawning via activation of
the OT and CRF neurons in the PVN.
 
Previous studies have indicated that yawning response is reproductively evoked by electrical or chemical stimulation of the medial parvocellular subdivision of the PVN [2,27,28,35]. Sato-Suzuki et al. [35] first reported that yawning response induced by the PVN stimulation is typically characterized by a single large inspiration with mouth opening that occurred after the depressor response and the arousal response, which is the stereotyped yawning response. In the present study, microinjection of L-glutamate into the CeA caused an initial depressor response and an arousal shift on the ECoG followed by a single large inspiration. These physiological responses by the CeA stimulation were qualitatively the same as the stereotyped yawning response induced by the PVN stimulation. Therefore, the CeA appears to be involved in the induction of the stereotyped yawning responses.
Although the neuronal mechanism involved in the induction of stereotyped yawning response by the CeA stimulation is unknown, previous studies have indicated that the OT and CRF neurons in the PVN are responsible for induction of the stereotyped yawning responses [1,2,18&endash;20]. Our immunohistochemistry data indicated activation of both OT and CRF neurons in the parvocellular subdivision of the PVN after microinjections of L-glutamate into the CeA, which induced stereotyped yawning responses. Thus, these data suggest that the CeA stimulation induces yawning responses via activation of OT and CRF neurons in the PVN. The possibility that the CeA may mediate activation of OT and CRF neurons in the PVN in induction of stereotyped yawning responses is supported by neuroanatomical evidence. Neuroanatomical studies have reported that the CeA neurons directly innervate the caudal lateral and medial parvocellular regions of the PVN [6,13,15], suggesting a possibility that the direct pathway from the CeA to the PVN may be involved in induction of stereotyped yawning responses. But we also consider another possibility that induction of stereotyped yawning responses might be mediated by indirect pathways from the CeA to the PVN via mesolimbic brain regions, including the ventral tegmental area (VTA) and bed nucleus of the stria terminals (BNST). The mesolimbic brain regions such as the VTA and BNST are anatomically connected with the CeA and PVN [8&endash;11] and have been reported to be involved in induction of yawning behavior by neuropharmacological studies [26,33,34,37], supporting the possibility for indirect pathways from the CeA to the PVN via the mesolimbic brain regions. Thus, it is possible that neuronal activation of the CeA directly or indirectly evoked activation of OT and CRF neurons in the parvocellular subdivision of the PVN, thereby inducing stereotyped yawning responses. However, our c-Fos immunoreactive data is correlative. Therefore, the neuronal pathway underlying yawning induced by neuronal activation of the CeA should be investigated using pharmacological and lesion studies in the near future.
 
The present study showed that chemical stimulation of the CeA could induce a stereotyped yawning response. However, it is noticed that the stereotyped yawning response induced by the CeA stimulation had a long latency when compared with that by the PVN stimulation. Furthermore, the occurrence rate of the stereotyped yawning responses by the CeA stimulation was lower than that by the PVN stimulation. The reasons why the CeA stimulation induced stereotyped yawning responses with delayed respiratory responses and low occurrence rate are unknown. Previous studies have demonstrated that neuronal structure in the medial parvocellular subdivision of the PVN is responsible for triggering the stereotyped yawning response [17&endash;19]. In the present study, we stimulated the CeA, which may not be the responsible region for triggering stereotyped yawning responses. We assume that the CeA is involved in the induction of the stereotyped yawning responses via neuronal activation of the PVN, and that the neuronal projections from the CeA to the PVN might be the key to understanding these delayed respiratory responses and low occurrence of the stereotyped yawning responses by the CeA stimulation. In addition, we cannot rule out the possibility that these delayed respiratory responses and low occurrence of the stereotyped yawning responses by the CeA stimulation may depend on brain state (i.e., neural activity induced by anesthesia), that is a limitation of anesthesia research.
 
What is the biological significance of yawning induced by neuronal activation of the CeA? Yawning is often observed not only in a state of boredom or drowsiness, but also in stressful emotional situations in humans and other animals. This suggests that yawning might be a behavior toward emotional stress. Clinical reports have shown that yawning is frequently observed in patients with anxiety and depression disorders, hysteria, and motion sickness [7,38]. Ethologists and psychologists have reported that primates commonly yawn when neigh- boring individuals display anxiety-like and sexual jealousy behaviors, which is indicative of yawning via emotional contagion [3,4]. In laboratory studies, it has reported that injection of anxiogenic compounds induce yawning behavior while anxiolytic drugs reduce frequency of yawning behavior in primates [12,22,24], and that auditory fear conditioning induce yawning behavior in rodents [21,29]. We have recently reported that emotional stress evoked by contextual fear conditioning induces yawning behavior, which is accompanied by neuronal activation of CeA as well as the PVN [21]. Furthermore, the CeA is known to be particularly essential for integration of emotional responses, and the PVN is primarily involved in behavioral, autonomic, and hormonal responses to stress. Most studies have reported that neuronal activation of the CeA connecting to the PVN is involved in secretion of stress hormones, activation of the autonomic nervous system, and expression of fear- and anxiety-like behaviors (see review [15],). Therefore, our findings suggest that yawning is one of these emotional behaviors. This suggestion may be supported by the involvements of not only neurotransmitters OT and CRF but also dopamine in expression of yawning behavior [1,2,18&endash;20,33], because OT, CRF, and dopamine are well known to modulate emotion processing including motivation/reward, adapt action, arousal, and stress response [5,14,16,32].
 
In summary, we observed that microinjection of L-glutamate into the CeA produced a stereotyped yawning response, i.e., fall in blood pressure and ECoG arousal preceding a large inspiration, in anesthetized and spontaneously breathing rats. Furthermore, activation of OT and CRF neurons in the PVN, which is responsible for induction of the stereotyped yawning response, were observed during yawning responses induced by the CeA stimulation. These results suggest that the CeA modulates induction of yawning via neuronal activation of the PVN and that yawning might be an emotional behavior.
 
 
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