Temporal and Spatial Influences on Fawn Summer Survival in Pronghorn Populations: Management Implications from Noninvasive Monitoring.

Monitoring vital rates allows managers to estimate trends in growth rates of ungulate populations. However, connecting the influence of nutrition on ungulate demography is challenging. Noninvasive sampling offers a low-cost, low-effort alternative for measuring nutritional indices, allowing for an increased understanding of the mechanistic relationships between environmental factors, nutrition, and specific population vital rates. We examined the temporal influence of intrinsic and extrinsic factors on pronghorn (Antilocapra americana) fawn recruitment. We collected fresh fecal samples from adult female pronghorn in five subpopulations spanning three sampling periods associated with critical maternal life-history stages (late gestation, early lactation, breeding season) for 2 years to investigate both intra- and interannual influences. Intrinsic factors were fecal glucocorticoid metabolites (FGMs), nutritional indices (fecal nitrogen (FN) and 2,6-diaminopimelic acid (DAPA)), and dietary composition (protein intake of forbs, graminoids, legumes, other, shrubs), while the extrinsic factor was vegetative greenness (normalized difference vegetation index (NDVI)). We found variations in DAPA, protein intake of forbs, variation in forb protein intake, and protein intake of legumes during late gestation positively influenced fawn recruitment. Fecal nitrogen during early lactation showed the strongest positive influence on the recruitment of any measured parameter. Finally, breeding season NDVI and the variation in DAPA values positively influenced the subsequent year's fawn recruitment. Our longitudinal study enabled us to investigate which parameter was most important to specific periods of fawn development and recruitment. We combined the results across five subpopulations, but interpretation and subsequent management decisions should be made at the subpopulation level such that pronghorn subpopulations with low recruitment can be positively influenced by increasing nitrogen on the landscape available to adult females during the early lactation period. As the use of noninvasive monitoring methods continues to expand, we believe our methodologies and results can be broadly applied to other ungulate monitoring programs.

Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

Geographic Distribution and Neuropathology of Elaeophora schneideri in Shiras Moose (Alces alces shirasi) in Idaho, USA.

Elaeophorosis, infection by the filarial worm Elaeophora schneideri, is a parasitic disease of wild ungulates in North America; however, our understanding of the relevance of E. schneideri to moose (Alces alces) morbidity and mortality is incomplete. Between March 2020 and July 2022, necropsy and histopathology were performed on 61 Shiras moose (Alces alces shirasi) in Idaho, US. Among the 41 adults (greater than 1 yr old), 21 moose were from northern Idaho, and 20 were from southeastern Idaho. Elaeophorosis was diagnosed in 24% (10 of 41). All 10 infected moose were from southeastern Idaho; none of the 21 moose from northern Idaho were infected. No juvenile moose (nine from northern and 11 from southeastern Idaho) were infected. Microfilariae were detected histologically in 9 of 10 infected moose, most consistently in brain tissue associated with lesions indicative of ischemic injury to the neuroparenchyma attributed to occlusion of arterioles and capillaries by microfilariae or fibrin thrombi, including edema, necrosis, and glial nodules. Microfilariae found in other tissues of the head, including the eye, tongue, and pinnae of some animals, as well as in lung, heart, liver, and kidney, typically were associated with inflammation. Three of the 10 infected moose had cropped ears attributed to elaeophorosis, and four exhibited abnormal behavior, which may have been due to neuropathology associated with E. schneideri microfilariae in the brain.

Seasonal shifts in pronghorn antelope (Antilocapra americana) diets under a new lens: Examining diet composition using a molecular technique.

Foraging is one of the most fundamental activities contributing to the maximization of an animal's fitness, and thus herbivores must optimize their diet selection and intake to meet their nutrient demands for survival, growth, and reproduction. Using plant DNA barcoding, we determined diet composition of five subpopulations of adult female pronghorn antelope (Antilocapra americana) grazing rangelands in southern and southeastern Idaho, USA. Fecal samples were collected for two years (2018-2019), and across metabolically-important adult female life history stages (late gestation, early lactation, breeding season). Plant DNA barcoding yielded 137 detected species within pronghorn diets across subpopulations and sampling periods with forbs being the most abundant. Pronghorn dietary functional group composition ranged from 52.2-60.3% from forbs followed by shrubs (22.6-28.2%), graminoids (8.7-15.7%), and legumes (5.5-9.6%). Dietary protein intake was also highest from forbs and ranged from 32.4-62.4% followed by graminoids (1.2-43.1%), shrubs (18.7-21.3%), and legumes (2.6-7.4%). We found significant intra- and interannual differences in the mean number of genera-based plant detections in pronghorn diets. Dietary protein intake of cultivated legumes (e.g., alfalfa [Medicago sativa] and sainfoin [Onobrychis viciifolia]) was lower than expected, ranging from <1.0-30.8%, suggesting that even within an agricultural-dominated landscape, factors other than plant nutritional composition contributed to pronghorn diets. Although the plant DNA barcoding technique exhibits limitations, it demonstrated potential for elucidating pronghorn dietary species richness, particularly for plants consumed in small proportions, as well as for observing temporal fluctuations in functional group composition and dietary protein intake explained through the interplay between environmental factors, plant chemical composition, and the animals' physiological needs.

Effects of large-scale disturbance on animal space use: Functional responses by greater sage-grouse after megafire.

Global change has altered the nature of disturbance regimes, and megafire events are increasingly common. Megafires result in immediate changes to habitat available to terrestrial wildlife over broad landscapes, yet we know surprisingly little about how such changes shape space use of sensitive species in habitat that remains. Functional responses provide a framework for understanding and predicting changes in space use following habitat alteration, but no previous studies have assessed functional responses as a consequence of megafire. We studied space use and tested for functional responses in habitat use by breeding greater sage-grouse (Centrocercus urophasianus) before and after landscape-level changes induced by a >40,000 ha, high-intensity megafire that burned sagebrush steppe in eastern Idaho, USA. We also incorporated functional responses into predictive resource selection functions (RSFs) to map breeding habitat before and after the fire. Megafire had strong effects on the distribution of available resources and resulted in context-dependent habitat use that was heterogeneous across different components of habitat. We observed functional responses in the use and selection of a variety of resources (shrubs and herbaceous vegetation) for both nesting and brood rearing. Functional responses in the use of nesting habitat were influenced by the overarching effect of megafire on vegetation, whereas responses during brood rearing appeared to be driven by individual variation in available resources that were conditional on nest locations. Importantly, RSFs built using data collected prior to the burn also had poor transferability for predicting space use in a post-megafire landscape. These results have strong implications for understanding and predicting how animals respond to a rapidly changing environment, given that increased severity, frequency, and extent of wildfire are consequences of global change with the capacity to reshape ecosystems. We therefore demonstrate a conceptual framework to better understand space use and aid habitat conservation for wildlife in a rapidly changing world.

Whiskers provide time-series of toxic and essential trace elements, Se:Hg molar ratios, and stable isotope values of an apex Antarctic predator, the leopard seal.

In an era of rapid environmental change and increasing human presence, researchers need efficient tools for tracking contaminants to monitor the health of Antarctic flora and fauna. Here, we examined the utility of leopard seal whiskers as a biomonitoring tool that reconstructs time-series of significant ecological and physiological biomarkers. Leopard seals (Hydrurga leptonyx) are a sentinel species in the Western Antarctic Peninsula due to their apex predator status and top-down effects on several Antarctic species. However, there are few data on their contaminant loads. We analyzed leopard seal whiskers (n = 18 individuals, n = 981 segments) collected during 2018-2019 field seasons to acquire longitudinal profiles of non-essential (Hg, Pb, and Cd) and essential (Se, Cu, and Zn) trace elements, stable isotope (ẟ15N and ẟ13C) values and to assess Hg risk with Se:Hg molar ratios. Whiskers provided between 46 and 286 cumulative days of growth with a mean ~ 125 days per whisker (n = 18). Adult whiskers showed variability in non-essential trace elements over time that could partly be explained by changes in diet. Whisker Hg levels were insufficient (<20 ppm) to consider most seals being at "high" risk for Hg toxicity. Nevertheless, maximum Hg concentrations observed in this study were greater than that of leopard seal hair measured two decades ago. However, variation in the Se:Hg molar ratios over time suggest that Se may detoxify Hg burden in leopard seals. Overall, we provide evidence that the analysis of leopard seal whiskers allows for the reconstruction of time-series ecological and physiological data and can be valuable for opportunistically monitoring the health of the leopard seal population and their Antarctic ecosystem during climate change.

Postoperative Stomach Volvulus and Pancreatitis Following a Sleeve Gastrectomy.

The laparoscopic sleeve gastrectomy is the most common bariatric surgery performed to promote weight loss and improve obesity-related comorbidities. As the number of patients undergoing sleeve gastrectomy increases, so does the prevalence of complications. It is crucial to recognize both common and unusual complications of sleeve gastrectomy to properly diagnose and manage them. We present a unique case of gastric outlet obstruction not visualized on initial imaging and acute pancreatitis following a sleeve gastrectomy. We recommend performing an endoscopy and ordering serum lipase levels in a patient with negative CT scans but persistent postoperative nausea, vomiting, and abdominal pain. The management of postoperative gastric outlet obstruction includes supportive care, balloon dilation of the stenotic area, or gastric bypass if symptoms persist.

Imaging the Aging Cochlea with Light-Sheet Fluorescence Microscopy.

Deafness is the most common sensory impairment, affecting approximately 5% or 430 million people worldwide as per the World Health Organization1. Aging or presbycusis is a primary cause of sensorineural hearing loss and is characterized by damage to hair cells, spiral ganglion neurons (SGNs), and the stria vascularis. These structures reside within the cochlea, which has a complex, spiral-shaped anatomy of membranous tissues suspended in fluid and surrounded by bone. These properties make it technically difficult to investigate and quantify histopathological changes. To address this need, we developed a light-sheet microscope (TSLIM) that can image and digitize the whole cochlea to facilitate the study of structure-function relationships in the inner ear. Well-aligned serial sections of the whole cochlea result in a stack of images for three-dimensional (3D) volume rendering and segmentation of individual structures for 3D visualization and quantitative analysis (i.e., length, width, surface, volume, and number). Cochleae require minimal processing steps (fixation, decalcification, dehydration, staining, and optical clearing), all of which are compatible with subsequent high-resolution imaging by scanning and transmission electron microscopy. Since all the tissues are present in the stacks, each structure can be assessed individually or relative to other structures. In addition, since imaging uses fluorescent probes, immunohistochemistry and ligand binding can be used to identify specific structures and their 3D volume or distribution within the cochlea. Here we used TSLIM to examine cochleae from aged mice to quantify the loss of hair cells and spiral ganglion neurons. In addition, advanced analyses (e.g., cluster analysis) were used to visualize local reductions of spiral ganglion neurons in Rosenthal's canal along its 3D volume. These approaches demonstrate TSLIM microscopy's ability to quantify structure-function relationships within and between cochleae.

Activity in a prefrontal-periaqueductal gray circuit overcomes behavioral and endocrine features of the passive coping stress response.

The question of how the brain links behavioral and biological features of defensive responses has remained elusive. The importance of this problem is underscored by the observation that behavioral passivity in stress coping is associated with elevations in glucocorticoid hormones, and each may carry risks for susceptibility to a host of stress-related diseases. Past work implicates the medial prefrontal cortex (mPFC) in the top-down regulation of stress-related behaviors; however, it is unknown whether such changes have the capacity to buffer against the longer-lasting biological consequences associated with aversive experiences. Using the shock probe defensive burying test in rats to naturalistically measure behavioral and endocrine features of coping, we observed that the active behavioral component of stress coping is associated with increases in activity along a circuit involving the caudal mPFC and midbrain dorsolateral periaqueductal gray (PAG). Optogenetic manipulations of the caudal mPFC-to-dorsolateral PAG pathway bidirectionally modulated active (escape and defensive burying) behaviors, distinct from a rostral mPFC-ventrolateral PAG circuit that instead limited passive (immobility) behavior. Strikingly, under conditions that biased rats toward a passive coping response set, including exaggerated stress hormonal output and increased immobility, excitation of the caudal mPFC-dorsolateral PAG projection significantly attenuated each of these features. These results lend insight into how the brain coordinates response features to overcome passive coping and may be of importance for understanding how activated neural systems promote stress resilience.

Synaptic Mechanisms Regulating Mood State Transitions in Depression.

Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, and generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees by all known antidepressants, suggesting that synaptic remodeling could play a key role in depression pathophysiology and antidepressant function. Still, it is unclear whether and precisely how synaptogenesis contributes to mood state transitions. Here, we review evidence supporting an emerging model in which depression is defined by a distinct brain state distributed across multiple stress-sensitive circuits, with neurons assuming altered functional properties, synapse configurations, and, importantly, a reduced capacity for plasticity and adaptation. Antidepressants act initially by facilitating plasticity and enabling a functional reconfiguration of this brain state. Subsequently, synaptogenesis plays a specific role in sustaining these changes over time.

The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits.

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary-adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation-but not inhibition-of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.

Evidence for Similar Prefrontal Structural and Functional Alterations in Male and Female Rats Following Chronic Stress or Glucocorticoid Exposure.

Previous work of ours and others has documented regressive changes in neuronal architecture and function in the medial prefrontal cortex (mPFC) of male rats following chronic stress. As recent focus has shifted toward understanding whether chronic stress effects on mPFC are sexually dimorphic, here we undertake a comprehensive analysis to address this issue. First, we show that chronic variable stress (14-day daily exposure to different challenges) resulted in a comparable degree of adrenocortical hyperactivity, working memory impairment, and dendritic spine loss in mPFC pyramidal neurons in both sexes. Next, exposure of female rats to 21-day regimen of corticosterone resulted in a similar pattern of mPFC dendritic spine attrition and increase in spine volume. Finally, we examined the effects of another widely used regimen, chronic restraint stress (CRS, 21-day of daily 6-h restraint), on dendritic spine changes in mPFC in both sexes. CRS resulted in response decrements in adrenocortical output (habituation), and induced a pattern of consistent, but less widespread, dendritic spine loss similar to the foregoing challenges. Our data suggest that chronic stress or glucocorticoid exposure induces a relatively undifferentiated pattern of structural and functional alterations in mPFC in both males and females.

Stenotrophomonas maltophilia infections: Clinical characteristics in a military trauma population.

Stenotrophomonas maltophilia is a pathogen with unique resistance patterns. We assessed 70 combat casualties with S. maltophilia clinical isolates to examine its role as a nosocomial pathogen in critically-ill trauma patients. Incidence density was 0.36 S. maltophilia infections per 100 patient-days (95% CI: 0.29-0.44). Patients predominantly had blast trauma (97%) and were critically injured (injury severity score [ISS] >25; 80%). Restricting to patients with ISS >15, 50 patients with S. maltophilia infections were compared to 441 patients with infections attributed to other gram-negative bacilli. Patients with S. maltophilia infections had significantly more operating room visits prior to isolation, traumatic or early surgical amputations, longer hospitalization (median 71 vs 47 days), and higher overall mortality (10% vs 2%; P = 0.01). Initial and serial (≥7 days between initial and subsequent isolation) S. maltophilia isolates had high susceptibility to trimethoprim-sulfamethoxazole and minocycline. Evaluation of newer agents awaiting CLSI breakpoints, including moxifloxacin, showed promising results.

Prevalence and Clinical Outcomes of Patients with Diabetic Ketoacidosis/Hyperglycemic Hyperosmolar Syndrome and COVID-19: A Systematic Review

@#BACKGROUND AND OBJECTIVES. Several reports have shown that coexistence of diabetes mellitus and COVID-19 is one of the risk factors for poor outcome and increased mortality. Rapid metabolic deterioration with development of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS) may result due to the acute insulin secretory capacity loss, stress condition and the cytokine storm. In this review, we aim to describe the prevalence of hyperglycemic crises(DKA/HHS) in patients with COVID-19 infection as well as their clinical outcomes. METHODS. An intensive search was done using the WebMD, PubMed, Medline and Google Scholar databases for articles published between December 2019 to October 2020 that identified the number of patients who developed DKA and/or HHS among those who were admitted for COVID-19. Their clinical outcomes were likewise described. RESULTS. This review included 4 articles in which individual quality was assessed. A total of 1282 patients were admitted for COVID-19 and the prevalence of DKA was 1.32%. HHS was not reported in any of the studies. Five (29.4%) of the patients with DKA and COVID-19 died and 12 (70.6%) recovered. CONCLUSIONS. A significant number of COVID-19 patients developed DKA and it is associated with a high mortality rate. This reimposes the need for an appropriate algorithm for the optimal management of concomitant COVID 19 and hyperglycemic crises to avoid morbidity and mortality. Additionally, there is paucity of large-scale studies describing the prevalence of DKA/HHS in patients with COVID-19.

Review of 18F-Fluciclovine PET for Detection of Recurrent Prostate Cancer.

Fluorine 18 (18F) fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC]) is a radiolabeled amino acid analog that takes advantage of the amino acid transport upregulation in several types of cancer cells. FACBC is taken up to a greater extent in prostate cancer cells than in surrounding normal tissue, providing an opportunity for its use in cases of this common cancer. In 2016, the U.S. Food and Drug Administration found the accuracy of FACBC PET to be superior to that of other molecular imaging techniques and subsequently granted approval for its use in PET of recurrent prostate cancer. As FACBC is an 18F radiotracer, an on-site cyclotron is not required for its production. This feature enables the widespread clinical availability of this agent and, in turn, an opportunity for improved patient care. The clinical pharmacology and imaging features of FACBC are reviewed, and the role of this agent in the imaging of recurrent prostate cancer, within the context of research that supports its effectiveness, is discussed. The administration of and image acquisition facilitated by using FACBC, as compared with 18F fluorodeoxyglucose, which is more widely used, are described. In addition, the criteria for interpreting FACBC imaging findings are outlined, with emphasis on common causes of false-positive and false-negative findings. ©RSNA, 2019.

Prefrontal-Bed Nucleus Circuit Modulation of a Passive Coping Response Set.

One of the challenges facing neuroscience entails localization of circuits and mechanisms accounting for how multiple features of stress responses are organized to promote survival during adverse experiences. The rodent medial prefrontal cortex (mPFC) is generally regarded as a key site for cognitive and affective information processing, and the anteroventral bed nuclei of the stria terminalis (avBST) integrates homeostatic information from a variety of sources, including the mPFC. Thus, we proposed that the mPFC is capable of generating multiple features (endocrine, behavioral) of adaptive responses via its influence over the avBST. To address this possibility, we first optogenetically inhibited input to avBST from the rostral prelimbic cortical region of mPFC and observed concurrent increases in immobility and hypothalamo-pituitary-adrenal (HPA) output in male rats during tail suspension, whereas photostimulation of this pathway decreased immobility during the same challenge. Anatomical tracing experiments confirmed projections from the rostral prelimbic subfield to separate populations of avBST neurons, and from these to HPA effector neurons in the paraventricular hypothalamic nucleus, and to aspects of the midbrain periaqueductal gray that coordinate passive defensive behaviors. Finally, stimulation and inhibition of the prelimbic-avBST pathway, respectively, decreased and increased passive coping in the shock-probe defensive burying test, without having any direct effect on active coping (burying) behavior. These results define a new neural substrate in the coordination of a response set that involves the gating of passive, rather than active, coping behaviors while restraining neuroendocrine activation to optimize adaptation during threat exposure.SIGNIFICANCE STATEMENT The circuits and mechanisms accounting for how multiple features of responses are organized to promote adaptation have yet to be elucidated. Our report identifies a prefrontal-bed nucleus pathway that organizes a response set capable of gating passive coping behaviors while concurrently restraining neuroendocrine activation during exposure to inescapable stressors. These data provide insight into the central organization of how multiple features of responses are integrated to promote adaptation during adverse experiences, and how disruption in one neural pathway may underlie a broad array of maladaptive responses in stress-related psychiatric disorders.

Anteroventral bed nuclei of the stria terminalis neurocircuitry: Towards an integration of HPA axis modulation with coping behaviors - Curt Richter Award Paper 2017.

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral responses to emotionally stressful experiences, and chronic disruption of these systems chronically is implicated in the pathogenesis of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA activity, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Moreover, information regarding how endocrine and behavioral responses are integrated has remained obscure. Here we summarize work from our laboratory showing that anteroventral (av) bed nuclei of the stria terminalis (BST) acts as a point of convergence between the limbic forebrain and PVH, receiving and coordinating upstream influences, and restraining HPA axis output in response to inescapable stressors. Recent studies highlight a more expansive modulatory role for avBST as one that coordinates HPA-inhibitory influences while concurrently suppressing passive behavioral responses via divergent pathways. avBST is uniquely positioned to convey endocrine and behavioral alterations resulting from chronic stress exposure, such as HPA axis hyperactivity and increased passive coping strategies, that may result from synaptic reorganization in upstream limbic cortical regions. We discuss how these studies give new insights into understanding the systems-level organization of stress response circuitry, the neurobiology of coping styles, and BST circuit dysfunction in stress-related psychiatric disorders.