As yawning is often observed in stressful or emotional situations such as tension and anxiety, this suggests that yawning can be considered to be an emotional behavior. However, the neural mechanisms ...underlying emotion-induced yawning remain unclear. It is well known that the hypothalamic paraventricular nucleus (PVN) is the most important brain structure for induction of yawning behavior. We previously showed that induction of yawning involves the central nucleus of the amygdala (CeA), as well as the PVN. Therefore, emotion-induced yawning could potentially be induced through activation of the direct/indirect neural pathways from the CeA to the PVN. Our present study used a combination of retrograde tracing (injection of Fluoro-Gold (FG) into the PVN) and c-Fos immunohistochemistry to examine the neural pathways that evoke emotion-induced yawning. We additionally performed lesion experiments on the CeA using ibotenic acid, a neurotoxin, to determine whether the CeA is involved in the induction of emotion-induced yawning. Emotional stress by fear conditioning induced yawning behavior, and induced expression of double-labeled cells for c-Fos and FG in the bed nucleus of the stria terminalis (BNST), but not in the CeA. Furthermore, the CeA lesions caused by ibotenic acid abolished the induction of emotion-induced yawning. These results suggest that a neural pathway from the CeA to the PVN via the BNST may be primarily involved in the induction of emotion-induced yawning behavior.
•We examined the neural pathways of emotion-induced yawning with a combination of tracing and immunohistochemistry.•Emotional stress by fear conditioning induced yawning behavior.•Indirect neural pathway from the CeA to the PVN is involved in the induction of emotion-induced yawning.•The CeA lesions caused by ibotenic acid abolished the induction of emotion-induced yawning.
•Neuronal activities to acute exercise at different intensities were examined.•Changes in anxiety- and depressive-like behaviors by acute exercise were assessed.•Acute exercise with mild or low ...stress induces antidepressant/anxiolytic effects.
Accumulating evidence suggests that physical exercise can reduce and prevent the incidence of stress-related psychiatric disorders, including depression and anxiety. Activation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is implicated in antidepressant/anxiolytic properties. In addition, the incidence and symptoms of these disorders may involve dysregulation of the hypothalamic–pituitary–adrenal axis that is initiated by corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Thus, it is possible that physical exercise produces its antidepressant/anxiolytic effects by affecting these neuronal activities. However, the effects of acute physical exercise at different intensities on these neuronal activation and behavioral changes are still unclear. Here, we examined the activities of 5-HT neurons in the DRN and CRF neurons in the PVN during 30min of treadmill running at different speeds (high speed, 25m/min; low speed, 15m/min; control, only sitting on the treadmill) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed the elevated plus maze test and the forced swim test to assess anxiety- and depressive-like behaviors, respectively. Acute treadmill running at low speed, but not high speed, significantly increased c-Fos expression in 5-HT neurons in the DRN compared to the control, whereas high-speed running significantly enhanced c-Fos expression in CRF neurons in the PVN compared with the control and low-speed running. Furthermore, low-speed running resulted in decreased anxiety- and depressive-like behaviors compared with high-speed running. These results suggest that acute physical exercise with mild and low stress can efficiently induce optimal neuronal activation that is involved in the antidepressant/anxiolytic effects.
•Microinjection of L-glutamate into the CeA caused the typical pattern of stereotyped yawning responses.•The CeA stimulation activated the neuronal activities of both OT and CRF neurons in the PVN, ...which are responsible for triggering yawning.•Yawning might be an emotional behavior, being based on neural mechanisms.
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.
We examined the activities of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) during ...acute treadmill running at different speeds (control, low, high) and durations (15, 30, 60 min) in male Wistar rats using c-Fos/5-HT or CRF immunohistochemistry. We also performed elevated plus maze test (EPM) and forced swim test (FST) after acute treadmill running in rats. Acute treadmill running at low speed, regardless of exercise duration, significantly increased c-Fos expression in 5-HT neurons in the DRN compared with controls, whereas high-speed running significantly activated 5-HT neurons only at 60-min duration. In contrast, c-Fos expression in CRF neurons in the PVN was enhanced in an intensity-dependent manner, regardless of exercise duration. c-Fos expression in 5-HT neurons in the DRN induced by the acute treadmill running for 30 or 60 min, but not 15 min, was positively correlated with the time spent on the open arms in the EPM and was negatively correlated with the immobility time in the FST. These results suggest an interaction between exercise intensity and duration on the antidepressant effects of acute physical exercise.
Increasing clinical evidence suggests that regular physical exercise can prevent or reduce the incidence of stress-related psychiatric disorders including depressive symptoms. Antidepressant effect ...of regular exercise may be implicated in monoaminergic transmission including serotonergic transmission, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis, but few general concepts regarding the optimal exercise regimen for stimulating neural mechanisms involved in antidepressant properties have been developed. Here, we examined how 4 weeks of treadmill running at different intensities (0, 15, 25 m/min, 60 min/day, 5 times/week) alters neuronal activity in the dorsal raphe nucleus (DRN), which is the major source of serotonin (5-HT) neurons in the central nervous system, and the hypothalamic paraventricular nucleus (PVN), in which corticotropin-releasing factor (CRF) neurons initiate the activation of the HPA axis, during one session of acute treadmill running at different speeds (0, 15, 25 m/min, 30 min) in male Wistar rats, using c-Fos immunohistochemistry. We also examined neurogenesis in the hippocampus using immunohistochemistry for doublecortin (DCX) and assessed depressive-like behavior using the forced swim test after regular exercise for 4 weeks. In the pre-training period, acute treadmill running at low speed, but not at high speed, increased c-Fos positive nuclei in the DRN compared with the sedentary control. The number of c-Fos positive nuclei in the PVN during acute treadmill running was increased in a running speed-dependent manner. Regular exercise for 4 weeks, regardless of the training intensity, induced an enhancement of c-Fos expression in the DRN during not only low-speed but also high-speed acute running, and generally reduced c-Fos expression in the PVN during acute running compared with pre-training. Furthermore, regular treadmill running for 4 weeks enhanced DCX immunoreactivity in the hippocampal dentate gyrus (DG), and resulted in decreased depressive-like behavior, regardless of the training intensity. These results suggest that long-term repeated exercise, regardless of the training intensity, improves depressive-like behavior through adaptive changes in the sensitivity of DRN and PVN neurons to acute exercise, and hippocampal neurogenesis.
Epidemiological studies showed the association between air pollution and dementia. A soluble fraction of particulate matters including polycyclic aromatic hydrocarbons (PAHs) is suspected to be ...involved with the adverse effects of air pollution on the central nervous system of humans. It is also reported that exposure to benzopyrene (BaP), which is one of the PAHs, caused deterioration of neurobehavioral performance in workers. The present study investigated the effect of BaP on noradrenergic and serotonergic axons in mouse brains. In total, 48 wild-type male mice (10 weeks of age) were allocated into 4 groups and exposed to BaP at 0, 2.88, 8.67 or 26.00 µg/mice, which is approximately equivalent to 0.12, 0.37 and 1.12 mg/kg bw, respectively, by pharyngeal aspiration once/week for 4 weeks. The density of noradrenergic and serotonergic axons was evaluated by immunohistochemistry in the hippocampal CA1 and CA3 areas. Exposure to BaP at 2.88 µg/mice or more decreased the density of noradrenergic or serotonergic axons in the CA1 area and the density of noradrenergic axons in the CA3 area in the hippocampus of mice. Furthermore, exposure to BaP dose-dependently upregulated
at 8.67 µg/mice or more, as well as upregulating
at 26 µg/mice,
at 2.88 and 26 µg/mice and
at 2.88 µg/mice. The results demonstrate that exposure to BaP induces degeneration of noradrenergic or serotonergic axons and suggest the involvement of proinflammatory or inflammation-related genes with BaP-induced neurodegeneration.
•Effects of the noradrenergic drug clonidine in the mPFC and AMY on VTE were tested.•Clonidine injection into either the mPFC or AMY impaired spatial choice performance.•Clonidine injection into the ...mPFC suppressed VTE in the early phase of the task.•Clonidine injection into the AMY hindered the decrease in VTE in the later phase of the task.
In uncertain choice situations, we deliberately search and evaluate possible options before taking an action. Once we form a preference regarding the current situation, we take an action more automatically and with less deliberation. In rats, the deliberation process can be seen in vicarious trial-and-error behavior (VTE), which is a head-orienting behavior toward options at a choice point. Recent neurophysiological findings suggest that VTE reflects the rat’s thinking about future options as deliberation, expectation, and planning when rats feel conflict. VTE occurs depending on the demand: an increase occurs during initial learning, and a decrease occurs with progression in learning. However, the brain circuit underlying the regulation of VTE has not been thoroughly examined. In situations in which VTE often appears, the medial prefrontal cortex (mPFC) and the amygdala (AMY) are crucial for learning and decision making. Our previous study reported that noradrenaline regulates VTE. Here, to investigate whether the mPFC and AMY are involved in regulation of VTE, we examined the effects of local injection of clonidine, an alpha2 adrenergic autoreceptor agonist, into either region in rats during VTE and choice behavior during a T-maze choice task. Injection of clonidine into either region impaired selection of the advantageous choice in the task. Furthermore, clonidine injection into the mPFC suppressed occurrence of VTE in the early phase of the task, whereas injection into the AMY inhibited the decrease in VTE in the later phase and thus maintained a high level of VTE throughout the task. These results suggest that the mPFC and AMY play a role in the increase and decrease in VTE, respectively, and that noradrenergic mechanisms mediate the dynamic regulation of VTE over experiences.
Several studies have demonstrated the possibility of positive effects of exposure to music during pregnancy on mental function in humans and animals. Although there remains a core belief in the ...positive effects of music during pregnancy, the underlying neurobehavioral mechanisms of these effects remain unknown. In this study, we aimed to clarify the relationship between maternal nurturing behavior and the oxytocinergic system to elucidate the effect of music on mental health during pregnancy in an experimental investigation using animal models. Pregnant rats were exposed to Mozart sonatas, and their nurturing behavior after delivery was assessed using behavioral analyses. The neural activities of the oxytocinergic system, which are associated with nurturing behavior, were investigated using FosB immunohistochemistry. Music during pregnancy significantly increased the licking behavior of mothers towards pups, which is representative of positive nurturing behavior. In contrast, this alteration in maternal behavior was shown to have no marked effect on the structure or activity of the oxytocinergic system. This study provided possible evidence that exposure to music during pregnancy had a positive effect on postnatal maternal behavior. The results also suggest that the oxytocinergic system, considered a strong candidate for the neural system that regulates maternal behavior, may not be associated with this behavioral change. Understanding the relationship between other neural systems, physiological responses, and nurturing behaviors will provide a more comprehensive explanation of the mechanisms by which music exposure during pregnancy has a positive effect on mental health.
•Pregnant rats were exposed to Mozart sonatas and their nurturing behavior was investigated.•Exposure to music during pregnancy has a positive effect on postnatal maternal behavior.•Maternal behavior had no marked effect on the structure or activity of the oxytocinergic neurons.
Prenatal music; Maternal behavior; Oxytocinergic system; FosB.
There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory ...bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 µg/m(3), 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust.
•We investigated the involvement of emotional stress in induction of yawning in rats.•Emotional stress induced yawning accompanied with neuronal activation of the PVN.•Emotional stress induced ...anxiety-related behavior.•Emotional stress caused neuronal activation of the CeA.
Yawning is often observed not only in a state of boredom or drowsiness but also in stressful emotional situations, suggesting that yawning is an emotional behavior. However, the neural mechanisms for yawning during stressful emotional situations have not been fully determined, though previous studies have suggested that both parvocellular oxytocin (OT) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) are responsible for induction of yawning. Thus, using ethological observations and c-Fos immunohistochemistry, we examined whether emotional stress evoked by classical fear conditioning is involved in induction of yawning behavior in freely moving rats. Emotional stress induced yawning behavior that was accompanied by anxiety-related behavior, and caused neuronal activation of the central nucleus of the amygdala (CeA), as well as increases in activity of both OT and CRF neurons in the PVN. These results suggest that emotional stress may induce yawning behavior, in which the neuronal activation of the CeA may have a key role.
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![Exposure to Benzo[a]pyrene ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1422-0067_1661-6596/small "Exposure to Benzo[a]pyrene Decreases Noradrenergic and Serotonergic Axons in Hippocampus of Mouse Brain")
