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Scientific Reports Apr 2024The natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and...
The natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and behavior. Aggressive and submissive behaviors assumed by animals through dominance interactions engage stress-dependent neural and hormonal systems that have been shown to correspond with social rank. Here, we examined the association between social dominance hierarchy status established within cages of group-housed mice and the expression of the stress peptide PACAP in the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). We also examined the relationship between social dominance rank and blood corticosterone (CORT) levels, body weight, motor coordination (rotorod) and acoustic startle. Male C57BL/6 mice were ranked as either Dominant, Submissive, or Intermediate based on counts of aggressive/submissive encounters assessed at 12 weeks-old following a change in homecage conditions. PACAP expression was significantly higher in the BNST, but not the CeA, of Submissive mice compared to the other groups. CORT levels were lowest in Submissive mice and appeared to reflect a blunted response following events where dominance status is recapitulated. Together, these data reveal changes in specific neural/neuroendocrine systems that are predominant in animals of lowest social dominance rank, and implicate PACAP in brain adaptations that occur through the development of social dominance hierarchies.
Topics: Animals; Male; Mice; Amygdala; Corticosterone; Mice, Inbred C57BL; Pituitary Adenylate Cyclase-Activating Polypeptide; Septal Nuclei; Social Dominance; Stress, Psychological
PubMed: 38637645
DOI: 10.1038/s41598-024-59459-9 -
Communications Biology Mar 2024The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria...
The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleep-wakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.
Topics: Wakefulness; Septal Nuclei; Sleep; GABAergic Neurons; Anesthesia, General
PubMed: 38503808
DOI: 10.1038/s42003-024-06028-5 -
Cell Reports Mar 2024Anorexia nervosa (AN) is a serious psychiatric disease, but the neural mechanisms underlying its development are unclear. A subpopulation of amygdala neurons, marked by...
Anorexia nervosa (AN) is a serious psychiatric disease, but the neural mechanisms underlying its development are unclear. A subpopulation of amygdala neurons, marked by expression of protein kinase C-delta (PKC-δ), has previously been shown to regulate diverse anorexigenic signals. Here, we demonstrate that these neurons regulate development of activity-based anorexia (ABA), a common animal model for AN. PKC-δ neurons are located in two nuclei of the central extended amygdala (EAc): the central nucleus (CeA) and oval region of the bed nucleus of the stria terminalis (ovBNST). Simultaneous ablation of CeA and ovBNST neurons prevents ABA, but ablating PKC-δ neurons in the CeA or ovBNST alone is not sufficient. Correspondingly, PKC-δ neurons in both nuclei show increased activity with ABA development. Our study shows how neurons in the amygdala regulate ABA by impacting both feeding and wheel activity behaviors and support a complex heterogeneous etiology of AN.
Topics: Animals; Protein Kinase C-delta; Anorexia; Neurons; Central Amygdaloid Nucleus; Neural Pathways; Septal Nuclei
PubMed: 38460131
DOI: 10.1016/j.celrep.2024.113933 -
Psychopharmacology Jun 2024This study aims to investigate the underlying neurobiological mechanisms that regulate natural reward seeking behaviors, specifically in the context of sexual behavior...
This study aims to investigate the underlying neurobiological mechanisms that regulate natural reward seeking behaviors, specifically in the context of sexual behavior and sucrose self-administration. The role of CaMKIIa+ neurons in the bed nucleus of the stria terminalis (BNST) was explored using chemogenetic silencing and -stimulation. Additionally, the study examined how these effects interacted with the internal state of the animals. Through detailed behavioral analysis, it was demonstrated that CaMKIIa+ neurons in the BNST play a significant role in the regulation of both sexual behavior and sucrose self-administration. Although the behavioral outcome measures differed between the two behaviors, the regulatory role of the CaMKIIa+ neurons in the BNST was found to converge on the modulation of the pacing of engagement in these behaviors in male rats. Moreover, our study confirmed that the internal physiological state of the animal affects how the BNST modulates these behaviors. These findings suggest that different types of natural rewards may recruit a similar brain circuitry to regulate the display of motivated behaviors. Overall, this research provides valuable insights into the neural mechanisms underlying natural reward seeking and sheds light on the interconnected nature of reward-related behaviors in male rats.
Topics: Animals; Reward; Septal Nuclei; Male; Rats; Neurons; Self Administration; Sexual Behavior, Animal; Rats, Sprague-Dawley; Sucrose; Motivation
PubMed: 38396196
DOI: 10.1007/s00213-024-06561-5 -
Addiction Biology Feb 2024Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for...
Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute for stress exposure to increase the latency to consume a palatable food in a novel context (hyponeophagia) and promote social avoidance in adult mice with AIE history. Given the dense connections between the BNST and the parabrachial nucleus (PBN), a region involved in mediating threat assessment and feeding behaviours, we hypothesized that increased negative affect-like behaviours would be associated with PBN activation. Our results revealed that the chemogenetic stimulation of the dorsolateral BNST induced hyponeophagia in females with AIE history, but not in female controls or males of either group. Social interaction remained unaffected in both sexes. Notably, this behavioural phenotype was associated with higher activation of calcitonin gene-related peptide and dynorphin cells in the PBN. These findings provide new insights into the neurobiological mechanisms underlying the development of negative affect in females and highlight the potential involvement of the BNST-PBN circuitry in regulating emotional responses to alcohol-related stimuli.
Topics: Male; Mice; Female; Animals; Parabrachial Nucleus; Alcoholism; Septal Nuclei; Ethanol
PubMed: 38380710
DOI: 10.1111/adb.13366 -
Neuropharmacology Mar 2024Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that...
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that intracerebroventricular administration of NPY reduces the expression of social fear via simultaneous activation of Y1 and Y2 receptors in a mouse model of social fear conditioning (SFC). In the present study, we investigated whether the anteroventral bed nucleus of the stria terminalis (BNSTav) mediates these effects of NPY, given the important role of BNSTav in regulating anxiety- and fear-related behaviors. We show that while NPY (0.1 nmol/0.2 μl/side) did not reduce the expression of SFC-induced social fear in male CD1 mice, it reduced the expression of both cued and contextual fear by acting on Y2 but not on Y1 receptors within the BNSTav. Prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μl/side) but not of the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μl/side) blocked the effects of NPY on the expression of cued and contextual fear. Similarly, NPY exerted non-social anxiolytic-like effects in the elevated plus maze test but not social anxiolytic-like effects in the social approach avoidance test by acting on Y2 receptors and not on Y1 receptors within the BNSTav. These results suggest that administration of NPY within the BNSTav exerts robust Y2 receptor-mediated fear-reducing and anxiolytic-like effects specifically in non-social contexts and add a novel piece of evidence regarding the neural underpinnings underlying the effects of NPY on conditioned fear and anxiety-like behavior.
Topics: Male; Mice; Animals; Neuropeptide Y; Receptors, Neuropeptide Y; Anti-Anxiety Agents; Septal Nuclei; Anxiety; Fear; Anterior Thalamic Nuclei
PubMed: 38218578
DOI: 10.1016/j.neuropharm.2024.109847 -
BioRxiv : the Preprint Server For... Dec 2023Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD)...
Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients may be used as biomarkers of brain degeneration. To characterize AD-specific PLR and its underlying neuromodulatory sources, we combined high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( ) and post-illumination pupil dilation recovery (amplitude, , and time, ). The -driven differential analysis revealed altered visual signal processing coupled with reduced thalamocortical activation in AD mice compared with the wild-type normal mice. In contrast, the post-illumination pupil dilation recovery-based fMRI highlighted multiple brain areas related to AD brain degeneration, including the cingulate cortex, hippocampus, septal area of the basal forebrain, medial raphe nucleus, and pontine reticular nuclei (PRN). Also, brain-wide functional connectivity analysis highlighted the most significant changes in PRN of AD mice, which serves as the major subcortical relay nuclei underlying oculomotor function. This work combined non-invasive pupil-fMRI measurements in preclinical models to identify pupillary biomarkers based on neuromodulatory dysfunction coupled with AD brain degeneration.
PubMed: 38187675
DOI: 10.1101/2023.12.20.572613 -
Cureus Dec 2023Lymphoepithelial carcinoma (LEC) is an uncommon neoplasm strongly associated with Epstein-Barr virus (EBV). LEC of the salivary glands (LECSG) is very rare: the most...
Lymphoepithelial carcinoma (LEC) is an uncommon neoplasm strongly associated with Epstein-Barr virus (EBV). LEC of the salivary glands (LECSG) is very rare: the most commonly affected site is the parotid gland, followed by the submandibular gland. This report describes the case of a 58-year-old man who presented with a left submandibular mass that had gradually increased in size over five years. On magnetic resonance imaging (MRI), the mass showed low apparent diffusion coefficient (ADC) values, rapid initial enhancement before reaching a plateau on dynamic contrast-enhanced MRI (DCE-MRI), and internal septal-like enhancement. Histopathologically, the tumor comprised polygonal or round tumor cells with atypical or pleomorphic nuclei and numerous lymphocytes, separated by heavy fibrosis. Immunohistological findings were positive for AE/AE3, CD20, and EBV-encoded small RNA in situ hybridization (EBER-ISH), consistent with LEC. A low ADC value with rapid initial enhancement before reaching a plateau on DCE-MRI was thought to reflect abundant cellular components with tumor neoangiogenesis, whereas internal septal-like enhancement reflects separating heavy fibrosis. To the best of our knowledge, this is the first case report describing ADC value and DCE-MRI findings of LECSG, and these findings can be considered characteristic MRI findings of LECSG.
PubMed: 38179348
DOI: 10.7759/cureus.49939 -
Neuroendocrinology 2024In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve...
INTRODUCTION
In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve nuclei that express Oxtr, the lateral septal nucleus (LS) and medial preoptic area (MPOA) are representative regions that control maternal behavior.
METHODS
We investigated the role of Oxtr- and Oxtr-expressing neurons, located in the LS and MPOA, in regulating maternal behavior by regulating Oxtr expression in a region-specific manner using recombinant mice and adeno-associated viruses. We quantified the prolactin (Prl) concentrations in the pituitary gland and plasma when Oxtr expression in the MPOA was reduced.
RESULTS
The endogenous Oxtr gene in the neurons of the LS did not seem to play an essential role in maternal behavior. Conversely, decreased Oxtr expression in the MPOA increased the frequency of pups being left outside the nest and reduced their survival rate. Deletion of Oxtr in MPOA neurons prevented elevation of Prl levels in plasma and pituitary at postpartum day 2.
DISCUSSION/CONCLUSION
Oxtr-expressing neurons in the MPOA are involved in the postpartum production of Prl. We confirmed the essential functions of Oxtr-expressing neurons and the Oxtr gene itself in the MPOA for the sustainability of maternal behavior, which involved Oxtr-dependent induction of Prl.
Topics: Animals; Receptors, Oxytocin; Maternal Behavior; Lactation; Preoptic Area; Female; Neurons; Prolactin; Mice; Septal Nuclei; Mice, Inbred C57BL; Mice, Transgenic; Oxytocin; Pituitary Gland
PubMed: 38071956
DOI: 10.1159/000535362 -
Neuroscience Jan 2024The paraventricular nucleus of the thalamus (PVT) sends dense projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the...
The paraventricular nucleus of the thalamus (PVT) sends dense projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral region of central nucleus of the amygdala (CeL). Projection specific modulation of these pathways has been shown to regulate appetitive and aversive behavioral responses. The present investigation applied an intersectional monosynaptic rabies tracing approach to quantify the brain-wide sources of afferent input to PVT neurons that primarily project to the NAcSh, BSTDL and CeL. The results demonstrate that these projection neurons receive monosynaptic input from similar brain regions. The prefrontal cortex and the ventral subiculum of the hippocampus were major sources of input to the PVT projection neurons. In addition, the lateral septal nucleus, thalamic reticular nucleus and the hypothalamic medial preoptic area, dorsomedial, ventromedial, and arcuate nuclei were sources of input. The subfornical organ, parasubthalamic nucleus, periaqueductal gray matter, lateral parabrachial nucleus, and nucleus of the solitary tract were consistent but lesser sources of input. This input-output relationship is consistent with recent observations that PVT neurons have axons that bifurcate extensively to divergently innervate the NAcSh, BSTDL and CeL.
Topics: Nucleus Accumbens; Central Amygdaloid Nucleus; Paraventricular Hypothalamic Nucleus; Hypothalamus; Neurons; Neural Pathways
PubMed: 38056620
DOI: 10.1016/j.neuroscience.2023.11.033