Central Amygdaloid Nucleus Research Articles

Effect of kynurenic acid on enzymatic activity of the DNA base excision repair pathway in specific areas of the sheep brain

Relatively low levels of antioxidant enzymes coupled with high oxygen metabolism result in the formation of numerous oxidative DNA damages in the tissues of the central nervous system. Recently, kynurenic acid (KYNA), knowns for its neuroprotective properties, has gained increasing attention in this context. Therefore, our hypothesis assumed that increased KYNA levels in the brain would positively influence mRNA expression of selected enzymes of the base excision repair pathway as well as enhance their efficiency in excising damaged nucleobases in specific areas of the sheep brain. The study was conducted on adult anestrous sheep (n = 18), in which two different doses of KYNA (20 and 100 μg/day) were infused into the third brain ventricle for three days. Molecular and biochemical analysis included the hypothalamus (preoptic and mediol-basal areas), hippocampus (CA3 field) and amygdala (central amygdaloid nucleus), dissected from the brain of sheep euthanized immediately after the last infusion. The results revealed a significant increase P < 0.001) in the relative mRNA abundance of N-methylpurine DNA glycosylase (MPG) following administration of both dose of KYNA across all examined tissues. The transcription of thymine-DNA glycosylase (TDG) increased significantly (P < 0.001) in all tissues in response to the lower KYNA dose compared to the control group. Moreover, 8-oxoguanine (8-oxoG) DNA glycosylase (OGG1) mRNA levels were also higher in both animal groups (P < 0.001). In addition, in the hypothalamus, hippocampus and amygdala, AP endonuclease 1 (APE1) mRNA expression increased under both doses of KYNA. Moreover, the both dose of KYNA significantly stimulated the efficiency of 8-oxoG excision in hypothalamus and amygdala (P < 0.05–0.001). The lower and higher doses of KYNA significantly influenced the effectiveness of εA and εC in all structures (P < 0.01–0.001). In conclusion, the favorable effect of KYNA in the brain may include the protection of genetic material in nerve and glial cells by stimulating the expression and efficiency of BER pathway enzymes.

Mapping of afferent and efferent connections of phenylethanolamine N-methyltransferase-expressing neurons in the nucleus tractus solitarii.

Phenylethanolamine N-methyltransferase (PNMT)-expressing neurons in the nucleus tractus solitarii (NTS) contribute to the regulation of autonomic functions. However, the neural circuits linking these neurons to other brain regions remain unclear. This study aims to investigate the connectivity mechanisms of the PNMT-expressing neurons in the NTS (NTSPNMT neurons). The methodologies employed in this study included a modified rabies virus-based retrograde neural tracing technique, conventional viral anterograde tracing, and immunohistochemical staining procedures. A total of 43 upstream nuclei projecting to NTSPNMT neurons were identified, spanning several key brain regions including the medulla oblongata, pons, midbrain, cerebellum, diencephalon, and telencephalon. Notably, dense projections to the NTSPNMT neurons were observed from the central amygdaloid nucleus, paraventricular nucleus of the hypothalamus, area postrema, and the gigantocellular reticular nucleus. In contrast, the ventrolateral medulla, lateral parabrachial nucleus, and lateral hypothalamic area were identified as the primary destinations for axon terminals originating from NTSPNMT neurons. Additionally, reciprocal projections were evident among 21 nuclei, primarily situated within the medulla oblongata. Our research findings demonstrate that NTSPNMT neurons form extensive connections with numerous nuclei, emphasizing their essential role in the homeostatic regulation of vital autonomic functions.

VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson’s disease

Parkinson's disease (PD) is a prevalent neurodegenerative disease and approximately one third of patients with PD are estimated to experience depression. Paraquat (PQ) is the most widely used herbicide worldwide and PQ exposure is reported to induce PD with depression. However, the specific brain region and neural networks underlying the etiology of depression in PD, especially in the PQ-induced model, have not yet been elucidated. Here, we report that the VGluT2-positive glutamatergic neurons in the paraventricular thalamic nucleus (PVT) promote depression in the PQ-induced PD mouse model. Our results show that PVTVGluT2 neurons are activated by PQ and their activation increases the susceptibility to depression in PD mice. Conversely, inhibition of PVTVGluT2 neurons reversed the depressive-behavioral changes induced by PQ. Similar to the effects of intervention the soma of PVTVGluT2 neurons, stimulation of their projections into the central amygdaloid nucleus (CeA) also strongly influenced depression in PD mice. PQ induced malfunctioning of the glutamate system and changes in the dendritic and synaptic morphology in the CeA through its role on PVTVGluT2 neuronal activation. In summary, our results demonstrate that PVTVGluT2 neurons are key neuronal subtypes for depression in PQ-induced PD and promote depression processes through the PVTVGluT2-CeA pathway.

Comparison of the connectivity of the posterior intralaminar thalamic nucleus and peripeduncular nucleus in rats and mice.

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.

Morphological heterogeneity of neurons in the human central amygdaloid nucleus.

The central amygdaloid nucleus (CeA) has an ancient phylogenetic development and functions relevant for animal survival. Local cells receive intrinsic amygdaloidal information that codes emotional stimuli of fear, integrate them, and send cortical and subcortical output projections that prompt rapid visceral and social behavior responses. We aimed to describe the morphology of the neurons that compose the human CeA (N = 8 adult men). Cells within CeA coronal borders were identified using the thionine staining and were further analyzed using the "single-section" Golgi method followed by open-source software procedures for two-dimensional and three-dimensional image reconstructions. Our results evidenced varied neuronal cell body features, number and thickness of primary shafts, dendritic branching patterns, and density and shape of dendritic spines. Based on these criteria, we propose the existence of 12 morphologically different spiny neurons in the human CeA and discuss the variability in the dendritic architecture within cellular types, including likely interneurons. Some dendritic shafts were long and straight, displayed few collaterals, and had planar radiation within the coronal neuropil volume. Most of the sampled neurons showed a few to moderate density of small stubby/wide spines. Long spines(thin and mushroom) were observed occasionally. These novel data address the synaptic processing and plasticity in the human CeA. Our morphological description can be combined with further transcriptomic, immunohistochemical, and electrophysiological/connectional approaches.It serves also to investigate how neurons are altered in neurological and psychiatric disorders with hindered emotional perception, in anxiety, following atrophy in schizophrenia, and along different stages of Alzheimer's disease.

Central administered xenin induced Fos expression in nesfatin-1 neurons in rats

Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system. After the intracerebroventricular administration of xenin on nesfain-1-like immunoreactivity (LI) neurons, we examined its effects on food intake and water intake in rats. As a result, Fos-LI neurons were observed in the organum vasculosum of the laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the arcuate nucleus (Arc), the lateral hypothalamic area (LHA), the central amygdaloid nucleus (CAN), the dorsal raphe nucleus (DR), the locus coeruleus (LC), the area postrema (AP) and the nucleus of the solitary tract (NTS). After the administration, the number of Fos-LI neurons was significantly increased in the LC and the OVLT, the MnPO, the SFO, the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. After the administration of xenin, we conducted double immunohistochemistry for Fos and nesfatin-1, and found that the number of nesfatin-1-LI neurons expressing Fos were significantly increased in the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. The pretreatment of nesfatin-1 antisense significantly attenuated this xenin-induced feeding suppression, while that of nesfatin-1 missense showed no improvement. These results indicate that central administered xenin may have anorexia effects associated with activated central nesfatin-1 neurons.

Whole-brain neural connectivity to cholinergic neurons in the nucleus basalis of Meynert.

The cholinergic neurons in the nucleus basalis of Meynert (NBM) are a key structure in cognition, the dysfunction of which is associated with various neurological disorders, especially dementias. However, the whole-brain neural connectivity to cholinergic neurons in the NBM remains to be further and comprehensively researched. Using virus-based, specific, retrograde, and anterograde tracing, we illustrated the monosynaptic inputs and axon projections of NBM cholinergic neurons in choline acetyltransferase (ChAT)-Cre transgenic mice. Our results showed that NBM cholinergic neurons received mainly inputs from the caudate putamen and the posterior limb of the anterior commissure in the subcortex. Moreover, the majority of cholinergic terminals from the NBM were observed in the cortex mantle, including the motor cortex, sensory cortex, and visual cortex. Interestingly, although NBM cholinergic neurons received input projections from the caudate putamen, interstitial nucleus of the posterior limb of the anterior commissure, and central amygdaloid nucleus, NBM cholinergic neurons sparsely sent axon projection to innervate these areas. Furthermore, primary motor cortex, secondary motor cortex, and primary somatosensory cortex received abundant inputs from the NBM but sent few outputs to the NBM. Taken together, our results reveal the detailed and specific connectivity of cholinergic neurons of the NBM and provide a neuroanatomic foundation for further studies to explore the important physiological functions of NBM cholinergic neurons.

Two Ascending Thermosensory Pathways from the Lateral Parabrachial Nucleus That Mediate Behavioral and Autonomous Thermoregulation.

Thermoregulatory behavior in homeothermic animals is an innate behavior to defend body core temperature from environmental thermal challenges in coordination with autonomous thermoregulatory responses. In contrast to the progress in understanding the central mechanisms of autonomous thermoregulation, those of behavioral thermoregulation remain poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates cutaneous thermosensory afferent signaling for thermoregulation. To understand the thermosensory neural network for behavioral thermoregulation, in the present study, we investigated the roles of ascending thermosensory pathways from the LPB in avoidance behavior from innocuous heat and cold in male rats. Neuronal tracing revealed two segregated groups of LPB neurons projecting to the median preoptic nucleus (MnPO), a thermoregulatory center (LPB→MnPO neurons), and those projecting to the central amygdaloid nucleus (CeA), a limbic emotion center (LPB→CeA neurons). While LPB→MnPO neurons include separate subgroups activated by heat or cold exposure of rats, LPB→CeA neurons were only activated by cold exposure. By selectively inhibiting LPB→MnPO or LPB→CeA neurons using tetanus toxin light chain or chemogenetic or optogenetic techniques, we found that LPB→MnPO transmission mediates heat avoidance, whereas LPB→CeA transmission contributes to cold avoidance. In vivo electrophysiological experiments showed that skin cooling-evoked thermogenesis in brown adipose tissue requires not only LPB→MnPO neurons but also LPB→CeA neurons, providing a novel insight into the central mechanism of autonomous thermoregulation. Our findings reveal an important framework of central thermosensory afferent pathways to coordinate behavioral and autonomous thermoregulation and to generate the emotions of thermal comfort and discomfort that drive thermoregulatory behavior.SIGNIFICANCE STATEMENT Coordination of behavioral and autonomous thermoregulation is important for maintaining thermal homeostasis in homeothermic animals. However, the central mechanism of thermoregulatory behaviors remains poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates ascending thermosensory signaling that drives thermoregulatory behavior. In this study, we found that one pathway from the LPB to the median preoptic nucleus mediates heat avoidance, whereas the other pathway from the LPB to the central amygdaloid nucleus is required for cold avoidance. Surprisingly, both pathways are required for skin cooling-evoked thermogenesis in brown adipose tissue, an autonomous thermoregulatory response. This study provides a central thermosensory network that coordinates behavioral and autonomous thermoregulation and generates thermal comfort and discomfort that drive thermoregulatory behavior.

Immunohistochemical Localization of MD2, a Co-Receptor of TLR4, in the Adult Mouse Brain.

Myeloid differentiation factor 2 (MD2) is a co-receptor of a classical proinflammatory protein TLR4 whose activation leads to neuroinflammation. It is widely accepted that TLR4 is expressed on the cell surface of microglia and astrocytes, and MD2 is expected to be expressed by these cells as well. However, our previous study showed that neurons from certain nuclei also expressed MD2. Whether MD2 is expressed by other brain nuclei is still unknown. It is the aim of the present study to map the distribution of MD2-positive cells in the adult mouse brain. Immunohistochemical staining against MD2 was completed to localize MD2-positive cells in the mouse brain by comparing the location of positive cells with the mouse brain atlas. MD2-positive cells were found in the majority of mouse brain nuclei with clusters of cells in the olfactory bulb, cortices, the red nucleus, and cranial nuclei. Subcortical nuclei had heterogeneous staining of MD2 with more prominent cells in the basolateral and the central amygdaloid nuclei. The ventral pallidum and the diagonal bands had positive cells with similar density and shape. Prominent cells were present in thalamic nuclei which were nearly homogeneous and in reticular formation of the brainstem where cells were dispersed with similar density. The hypothalamus had fewer outstanding cells compared with the thalamus. The red nucleus, the substantia nigra, and the ventral tegmental area in the pretectum had outstanding cells. Motor cranial nuclei also had outstanding MD2-positive cells, whereas raphe, sensory cranial, and deep cerebellar nuclei had MD2-positive cells with moderate density. The presence of MD2 in these nuclei may suggest the involvement of MD2 in their corresponding physiological functions.

Androgen receptors in the forebrain: A study in adult male cats.

Androgens and their receptors are present throughout the body. Various structures such as muscles, genitals, and prostate express androgen receptors. The central nervous system also expresses androgen receptors. Androgens cross the blood-brain barrier to reach these central areas. In the central nervous system, androgens are involved in multiple functions. The current study investigated in which forebrain areas androgens are expressed in the male cat. Androgen receptor immunoreactive (AR-IR) nuclei were plotted and the results were quantified with a Heidelberg Topaz II + scanner and Linocolor 5.0 software. The density and intensity of the labeled cells were the main outcomes of interest. The analysis revealed a dense distribution of AR-IR nuclei in the preoptic area, periventricular complex of the hypothalamus, posterior hypothalamic area, ventromedial hypothalamic, parvocellular hypothalamic, infundibular, and supramammillary nucleus. Numerous AR-IR cells were also observed in the dorsal division of the anterior olfactory nucleus, lateral septal nucleus, medial and lateral divisions of the bed nucleus of the stria terminalis, lateral olfactory tract nucleus, anterior amygdaloid area, and the central and medial amygdaloid nuclei. AR-IR nuclei were predominantly observed in areas involved in autonomic and neuroendocrinergic responses which are important for many physiological processes and behaviors.

Developing the theory of the extended amygdala with the use of the cupric-silver technique

ABSTRACT The amygdaloid complex is a crucial component of the basal forebrain that participates in the modulation of many homeostatic functions, emotional behaviors, and learning. These features require a widespread pattern of connections with several brain structures. In the past, the amygdaloid complex was divided into corticomedial and basolateral groups. The existence of a neuronal continuum linking the central amygdaloid nucleus to the lateral bed nucleus of stria terminalis through the subpallidal area was first revealed by José de Olmos (1932–2008) with the aid of his cupric-silver technique. This observation gave birth to the concept of the extended amygdala, a conceptual framework that is useful for understanding the anatomofunctional organization of the amygdaloid complex, with relevance for basic neuroscience and clinical interventions. Traditional tract-tracing staining methods were complicated and tedious to reproduce. Axonal terminal endings were lost among a myriad of normal fibers. The need to visualize these terminals drove de Olmos to develop cupric-silver methods that revealed disintegrating synaptic terminals, without staining normal fibers. In this article, we describe the historical events leading to the development of the cupric-silver technique that evolved into the amino-cupric-silver technique, which developed hand-in-hand over the years.

Reduced mechanical hypersensitivity by inhibition of the amygdala in experimental neuropathy: Sexually dimorphic contribution of spinal neurotransmitter receptors

Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male and female rats with spared nerve injury (SNI) model of neuropathy. SNI induced mechanical hypersensitivity that was stronger in females. Reversible blocking of the CeA with muscimol (GABAA receptor agonist) induced a reduction of mechanical hypersensitivity that did not differ between males and females. Following spinal co-administration of atipamezole (α2-adrenoceptor antagonist), the reduction of mechanical hypersensitivity by CeA muscimol was attenuated more in males than females. In contrast, following spinal co-administration of raclopride (dopamine D2 receptor antagonist) the reduction of hypersensitivity by CeA muscimol was attenuated more in females than males. The reduction of mechanical hypersensitivity by CeA muscimol was equally attenuated in males and females by spinal co-administration of WAY-100635 (5-HT1A receptor antagonist) or bicuculline (GABAA receptor antagonist). The CeA muscimol induced attenuation of ongoing pain-like behavior (conditioned place preference test) that was reversed by spinal co-administration of atipamezole in both sexes. The results support the hypothesis that CeA contributes to mechanical hypersensitivity and ongoing pain-like behavior in SNI males and females. Disinhibition of descending controls acting on spinal α2-adrenoceptors, 5-HT1A, dopamine D2 and GABAA receptors provides a plausible explanation for the reduction of mechanical hypersensitivity by CeA block in SNI. The involvement of spinal dopamine D2 receptors and α2-adrenoceptors in the CeA muscimol-induced reduction of mechanical hypersensitivity is sexually dimorphic, unlike that of spinal α2-adrenoceptors in the reduction of ongoing neuropathic pain.

Effects of neonatal rearing by different types of foster mother on the distribution of corticotropin-releasing factor neurons in the central amygdaloid nucleus in rats.

The mother-child relationship of newborns plays an essential role in the development of the central nervous system, and an inadequate relationship, such as mother-child separation, can cause deficits of mental function in adulthood. However, insufficient research has examined the effects of foster mothers. We assigned some neonatal rats to one of two foster mothers: one that was lactating and feeding her first litter (FL group) and one that had one previous experience of childbirth and feeding but no current litter (FE group). Other pups were raised by their own mother (OM group) or subjected to maternal separation (MS group). Pups were placed with the foster mother (FL and FE groups) or separated from their mother (MS group) for 3h/day on postnatal days 1-20. At age 6weeks, each group was divided into two subgroups, one with 30min of acute restraint stress loading (FL-R, FE-R, OM-R, and MS-R) and one without it (FL, FE, OM, and MS). Then, we compared the density of corticotropin-releasing factor-immunoreactive (CRF-ir) neurons in the central amygdaloid nucleus (CeA). The density of CRF-ir neurons in the CeA was significantly lower in the FL-R and MS-R subgroups than in the FL and MS subgroups, respectively. The results suggest that differences in care received during the neonatal period affect maturation of CRF neurons in the CeA and may have negative effects on the synthesis and release of CRF.

The role of central amygdaloid nucleus in regulating the nongenomic effect of aldosterone on sodium intake in the nucleus tractus solitary

ObjectiveThe central nucleus of the amygdala (CeA) has dense downward fiber projections towards the nucleus tractus solitary (NTS) and can modulate the activity of NTS taste neurons. However, whether CeA affects the nongenomic role of aldosterone (ALD) in regulating sodium intake at the NTS level remains unclear.MethodsFirst, 40 adult male Sprague Dawley rats were divided into five groups, referring to different concentrations of ALD, to observe the sodium intake pattern compared with the vehicle (n = 8). ALD, the mineralocorticoid receptor antagonist spironolactone (SPI), and ALD + SPI were injected into the NTS. Then, the rats were divided into four groups (n = 16): bilateral/unilateral CeA electrolytic lesions, bilateral/unilateral CeA sham lesions. After recovery, one stainless steel 23‐gauge cannula with two tubes was implanted into the rat NTS, and all rats underwent a recovery period of 7 days. Then, each group was divided into two subgroups that received aldosterone or control solution injection, and the cumulative intake of 0.3 mol/L NaCl solution was recorded within 30 min.ResultsBilateral CeA lesion eliminated the increased 0.3 mol/L NaCl intake induced by aldosterone microinjected into the NTS (CeA lesion: 0.3 ± 0.04 ml/30 min vs. sham lesion: 1.3 ± 0.3 ml/30 min). Unilateral CeA lesion reduced the increased NaCl intake induced by aldosterone microinjected into the NTS compared with the control group (p < .05) in the first 15 min but not in 15–30 min (p > .05). In sham lesion rats, aldosterone (5 ng/0.1 μl) still induced a significant increase in NaCl intake (aldosterone: 1.3 ± 0.3 ml/30 min vs. control: 0.25 ± 0.02 ml/30 min) (p < .05).ConclusionThe results verified that the complete CeA may play an important role in aldosterone to regulate the nongenomic effect on rapid sodium intake.

The brain of the tree pangolin (Manis tricuspis). VII. The amygdaloid body.

Here, we describe the cytoarchitecture and chemoarchitecture of the amygdaloid body of the tree pangolin. Our definition of the amygdaloid body includes the pallial portions of the amygdala, and the centromedial group that is a derivative of the subpallium and part of the extended amygdala. The remainder of the extended amygdala is not described herein. Within the amygdaloid body of the tree pangolin, we identified the basolateral group (composed of the lateral, basal, and accessory basal amygdaloid nuclei), the superficial, or cortical nuclei (the anterior and posterior cortical nuclei, the periamygdaloid cortex, and nuclei of the olfactory tract), the centromedial group (the central amygdaloid nucleus and the medial nuclear cluster), and other amygdaloid nuclei (the anterior amygdaloid area, the amygdalohippocampal area, the intramedullary group, and intercalated islands). The location within and relative to each other within the amygdaloid body and the internal subdivisions of these groups were very similar to that reported in other mammalian species, with no clearly derived features specific to the tree pangolin. The only variation was the lack of an insular appearance of the intercalated islands, which in the tree pangolin were observed as a continuous band of neurons located dorsomedial to the basolateral group similar in appearance to and almost continuous with the intramedullary group. In carnivores, the closest relatives of the pangolins, and laboratory rats, a similar appearance of portions of the intercalated islands has been noted.

Inflammatory Stress Induced by Intraperitoneal Injection of LPS Increases Phoenixin Expression and Activity in Distinct Rat Brain Nuclei.

Due to phoenixin’s role in restraint stress and glucocorticoid stress, as well as its recently shown effects on the inflammasome, we aimed to investigate the effects of lipopolysaccharide (LPS)-induced inflammatory stress on the activity of brain nuclei-expressing phoenixin. Male Sprague Dawley rats (n = 6/group) were intraperitoneally injected with either LPS or control (saline). Brains were processed for c-Fos and phoenixin immunohistochemistry and the resulting slides were evaluated using ImageJ software. c-Fos was counted and phoenixin was evaluated using densitometry. LPS stress significantly increased c-Fos expression in the central amygdaloid nucleus (CeM, 7.2-fold), supraoptic nucleus (SON, 34.8 ± 17.3 vs. 0.0 ± 0.0), arcuate nucleus (Arc, 4.9-fold), raphe pallidus (RPa, 5.1-fold), bed nucleus of the stria terminalis (BSt, 5.9-fold), dorsal motor nucleus of the vagus nerve (DMN, 89-fold), and medial part of the nucleus of the solitary tract (mNTS, 121-fold) compared to the control-injected group (p < 0.05). Phoenixin expression also significantly increased in the CeM (1.2-fold), SON (1.5-fold), RPa (1.3-fold), DMN (1.3-fold), and mNTS (1.9-fold, p < 0.05), leading to a positive correlation between c-Fos and phoenixin in the RPa, BSt, and mNTS (p < 0.05). In conclusion, LPS stress induces a significant increase in activity in phoenixin immunoreactive brain nuclei that is distinctively different from restraint stress.

Efferent and afferent connections of supratrigeminal neurons conveying orofacial muscle proprioception in rats.

The supratrigeminal nucleus (Su5) is a key structure for controlling jaw movements; it receives proprioceptive sensation from jaw-closing muscle spindles (JCMSs) and sends projections to the trigeminal motor nucleus (Mo5). However, the central projections and regulation of JCMS proprioceptive sensation are not yet fully understood. Therefore, we aimed to reveal the efferent and afferent connections of the Su5 using neuronal tract tracings. Anterograde tracer injections into the Su5 revealed that the Su5 sends contralateral projections (or bilateral projections with a contralateral predominance) to the Su5, basilar pontine nuclei, pontine reticular nucleus, deep mesencephalic nucleus, superior colliculus, caudo-ventromedial edge of the ventral posteromedial thalamic nucleus, parafascicular thalamic nucleus, zona incerta, and lateral hypothalamus, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) to the intertrigeminal region, trigeminal oral subnucleus, dorsal medullary reticular formation, and hypoglossal nucleus as well as the Mo5. Retrograde tracer injections into the Su5 demonstrated that the Su5 receives bilateral projections with a contralateral predominance (or contralateral projections) from the primary and secondary somatosensory cortices, granular insular cortex, and Su5, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) from the dorsal peduncular cortex, bed nuclei of stria terminalis, central amygdaloid nucleus, lateral hypothalamus, parasubthalamic nucleus, trigeminal mesencephalic nucleus, parabrachial nucleus, juxtatrigeminal region, trigeminal oral and caudal subnuclei, and dorsal medullary reticular formation. These findings suggest that the Su5, which receives JCMS proprioception, has efferent and afferent connections with multiple brain regions that are involved in emotional and autonomic functions as well as orofacial motor functions.

Chronic lithium exposure attenuates ketamine-induced mania-like behavior and c-Fos expression in the forebrain of mice

Ketamine, a dissociative anaesthetic, has been used in the treatment of major depressive disorder (MDD) as a rapid acting antidepressant drug. Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in MDD patients. Lithium is a well-known mood stabilizer and has been widely used for the treatment of mania. It is not fully understood which forebrain regions are involved in ketamine- and lithium-induced expression of c-Fos. Therefore, our aim was to investigate the effect of chronic lithium treatment on mania-like behavior and c-Fos expression in the mouse forebrain activated by a single administration of ketamine. In the open field test, our results showed that ketamine significantly increased the total distance and total cumulative duration of movement in mice, while chronic lithium could attenuate these effects of ketamine. In addition, acute ketamine induced higher c-Fos expression in the lateral septal nucleus, hypothalamus, amygdala, and hippocampus of mice in the treatment group compared to those in the control group. However, chronic lithium inhibited the significant increase in c-Fos-immunoreactive neurons following acute ketamine administration in the dentate gyrus of the hippocampus, field CA1 of the hippocampus, dorsal subiculum, ventral subiculum, ventral subiculum, central amygdaloid nucleus and basolateral amygdaloid nucleus. In summary, our research shows that pretreatment with lithium moderates the effects of acute ketamine administration on mania-like behavior and c-Fos expression in the forebrain. These findings could be helpful in better understanding the episodes of mania related to ketamine treatment for MDD and bipolar disorder.

Increased substance P-like immunoreactivities in parabrachial and amygdaloid nuclei in a rat model with masticatory myofascial pain.

This study explores the involvement of substance P (SP) in the parabrachial nucleus (PBN) and central amygdaloid nucleus (CeA) in the nociception-emotion link and of rats with masticatory myofascial pain (MMP) induced by chronic tetanic eccentric muscle contraction. A total of 18 rats were randomly and equally assigned for MMP (MMP group) and sham-MMP induction (sMMP group). MMP was induced by electrical-stimulated repetitive tetanic eccentric contraction of the masseter muscle for 14 consecutive days. Myofascial trigger points in the masseter muscle were identified by palpable taut bands, increased prevalence of endplate noise (EPN), focal hypoechoic nodules on ultrasound and restricted jaw opening. All animals were killed for morphological and SP immunohistochemical analyses. Chronic tetanic eccentric contraction induced significantly thicker masseter muscle confirmed by hypoechogenicity, increased prevalence and amplitudes of EPN, and limited jaw opening. Immunohistochemically, the SP-like positive neurons increased significantly in PBN and CeA of the MMP group. Our results suggested that MMP increases the SP protein levels in PBN and CeA, which play important roles in MMP-mediated chronic pain processing as well as MMP-related emotional processes.

Suppression of the Swallowing Reflex during Rhythmic Jaw Movements Induced by Repetitive Electrical Stimulation of the Dorsomedial Part of the Central Amygdaloid Nucleus in Rats.

A previous study indicated that the swallowing reflex is inhibited during rhythmic jaw movements induced by electrical stimulation of the anterior cortical masticatory area. Rhythmic jaw movements were induced by electrical stimulation of the central amygdaloid nucleus (CeA). The swallowing central pattern generator is the nucleus of the solitary tract (NTS) and the lateral reticular formation in the medulla. Morphological studies have reported that the CeA projects to the NTS and the lateral reticular formation. It is therefore likely that the CeA is related to the control of the swallowing reflex. The purpose of this study was to determine if rhythmic jaw movements driven by CeA had inhibitory roles in the swallowing reflex induced by electrical stimulation of the superior laryngeal nerve (SLN). Rats were anesthetised with urethane. The SLN was solely stimulated for 10 s, and the swallowing reflex was recorded (SLN stimulation before SLN + CeA stimulation). Next, the SLN and the CeA were electrically stimulated at the same time for 10 s, and the swallowing reflex was recorded during rhythmic jaw movements (SLN + CeA stimulation). Finally, the SLN was solely stimulated (SLN stimulation following SLN + CeA stimulation). The number of swallows was reduced during rhythmic jaw movements. The onset latency of the first swallow was significantly longer in the SLN + CeA stimulation than in the SLN stimulation before SLN + CeA stimulation and SLN stimulation following SLN + CeA stimulation. These results support the idea that the coordination of swallowing reflex with rhythmic jaw movements could be regulated by the CeA.