Social reactivation of fear engrams enhances memory recall.

For group-living animals, the social environment provides salient experience that can weaken or strengthen aspects of cognition such as memory recall. Although the cellular substrates of individually acquired fear memories in the dentate gyrus (DG) and basolateral amygdala (BLA) have been well-studied and recent work has revealed circuit mechanisms underlying the encoding of social experience, the processes by which social experience interacts with an individual's memories to alter recall remain unknown. Here we show that stressful social experiences enhance the recall of previously acquired fear memories in male but not female mice, and that social buffering of conspecifics' distress blocks this enhancement. Activity-dependent tagging of cells in the DG during fear learning revealed that these ensembles were endogenously reactivated during the social experiences in males, even after extinction. These reactivated cells were shown to be functional components of engrams, as optogenetic stimulation of the cells active during the social experience in previously fear-conditioned and not naïve animals was sufficient to drive fear-related behaviors. Taken together, our findings suggest that social experiences can reactivate preexisting engrams to thereby strengthen discrete memories.

Basolateral Amygdala Astrocytes Are Engaged by the Acquisition and Expression of a Contextual Fear Memory.

Astrocytes are key cellular regulators within the brain. The basolateral amygdala (BLA) is implicated in fear memory processing, yet most research has entirely focused on neuronal mechanisms, despite a significant body of work implicating astrocytes in learning and memory. In the present study, we used in vivo fiber photometry in C57BL/6J male mice to record from amygdalar astrocytes across fear learning, recall, and three separate periods of extinction. We found that BLA astrocytes robustly responded to foot shock during acquisition, their activity remained remarkably elevated across days in comparison to unshocked control animals, and their increased activity persisted throughout extinction. Further, we found that astrocytes responded to the initiation and termination of freezing bouts during contextual fear conditioning and recall, and this behavior-locked pattern of activity did not persist throughout the extinction sessions. Importantly, astrocytes do not display these changes while exploring a novel context, suggesting that these observations are specific to the original fear-associated environment. Chemogenetic inhibition of fear ensembles in the BLA did not affect freezing behavior or astrocytic calcium dynamics. Overall, our work presents a real-time role for amygdalar astrocytes in fear processing and provides new insight into the emerging role of these cells in cognition and behavior.SIGNIFICANCE STATEMENT We show that basolateral amygdala astrocytes are robustly responsive to negative experiences, like shock, and display changed calcium activity patterns through fear learning and memory. Additionally, astrocytic calcium responses become time locked to the initiation and termination of freezing behavior during fear learning and recall. We find that astrocytes display calcium dynamics unique to a fear-conditioned context, and chemogenetic inhibition of BLA fear ensembles does not have an impact on freezing behavior or calcium dynamics. These findings show that astrocytes play a key real-time role in fear learning and memory.

An expert review of environmental heat exposure and stillbirth in the face of climate change: Clinical implications and priority issues.

Exposure to extreme heat in pregnancy increases the risk of stillbirth. Progress in reducing stillbirth rates has stalled, and populations are increasingly exposed to high temperatures and climate events that may further undermine health strategies. This narrative review summarises the current clinical and epidemiological evidence of the impact of maternal heat exposure on stillbirth risk. Out of 20 studies, 19 found an association between heat and stillbirth risk. Recent studies based in low- to middle-income countries and tropical settings add to the existing literature to demonstrate that all populations are at risk. Additionally, both short-term heat exposure and whole-pregnancy heat exposure increase the risk of stillbirth. A definitive threshold of effect has not been identified, as most studies define exposure as above the 90th centile of the usual temperature for that population. Therefore, the association between heat and stillbirth has been found with exposures from as low as >12.64°C up to >46.4°C. The pathophysiological pathways by which maternal heat exposure may lead to stillbirth, based on human and animal studies, include both placental and embryonic or fetal impacts. Although evidence gaps remain and further research is needed to characterise these mechanistic pathways in more detail, preliminary evidence suggests epigenetic changes, alteration in imprinted genes, congenital abnormalities, reduction in placental blood flow, size and function all play a part. Finally, we explore this topic from a public health perspective; we discuss and evaluate the current public health guidance on minimising the risk of extreme heat in the community. There is limited pregnancy-specific guidance within heatwave planning, and no evidence-based interventions have been established to prevent poor pregnancy outcomes. We highlight priority research questions to move forward in the field and specifically note the urgent need for evidence-based interventions that are sustainable.

Automated, cryogen-free headspace-trap with gas chromatography-mass spectrometry analysis of ethylene oxide and 2-chloroethanol as residual fumigants in foods.

Ethylene oxide (EtO), although banned for use, is still being detected in foodstuffs that have been fumigated to eradicate pests during storage and transport. Residual levels over the European Union's (EU) maximum residue limit (MRL) pose severe health concerns. Recent detection of EtO and its by-product 2-chloroethanol (2-CE) at alarming levels have led to product recalls throughout the EU. Here, a simple, automated headspace (HS)-trap method for the simultaneous determination of EtO and its derivative 2-CE by gas chromatography-mass spectrometry (GC-MS) at the required MRL of ≤ 0.05 mg/kg has been implemented. Syringe-based HS combined with backflushed trapping technology provided enrichment of multiple extractions from the same sample vial (known as multi-step enrichment or MSE®) to increase sensitivity for EtO and 2-CE analysis by GC-MS using single-ion-monitoring (SIM) mode. Method detection limits (MDLs) of 0.00059 mg/kg and 0.00219 mg/kg for EtO and 2-CE, respectively, were obtained without the need for manual handling, solvent extraction or derivatization methods. Recoveries were shown to average (n = 5) at 98% and 107% for EtO and 2-CE, respectively, and the reproducibility was <10% for both compounds.

Multi-professional perspectives to reduce moral distress: A qualitative investigation.

BACKGROUND: Encounters of moral distress have long-term consequences on healthcare workers' physical and mental health, leading to job dissatisfaction, reduced patient care, and high levels of burnout, exhaustion, and intentions to quit. Yet, research on approaches to ameliorate moral distress across the health workforce is limited. RESEARCH OBJECTIVE: The aim of our study was to qualitatively explore multi-professional perspectives of healthcare social workers, chaplains, and patient liaisons on ways to reduce moral distress and heighten well-being at a southern U.S. academic medical center. PARTICIPANTS & RESEARCH CONTEXT: Purposive sampling and chain-referral methods assisted with recruitment through hospital listservs, staff meetings, and newsletters. Interested participants contacted the principal investigator and all interviews were conducted in-person. Consent was attained prior to interviews. All interviews were recorded and transcribed verbatim. RESEARCH DESIGN: Directed content analysis was used to deductively organize codes and to develop themes in conjunction with the National Academy of Medicine's National Plan for Health Workforce Well-Being. Rigor was attained through peer-debriefing, data triangulation methods, and frequent research team meetings. ETHICAL CONSIDERATIONS: Ethics approval was obtained from the university and medical center institutional review boards. FINDINGS: Themes demonstrate that rather than offering interventions in the aftermath of moral distress, multilevel daily practices ought to be considered that pre-emptively identify and reduce morally distressing encounters through (1) the care team, (2) management and leadership, and (3) the health care industry. Strategies include interdisciplinary decision-making, trusting managerial relationships, and organizational policies and practices that explicitly invest in mental health promotion and diverse leadership opportunities. CONCLUSION: Moral distress interventions ought to target short-term stress reactions while also addressing the long-term impacts of moral residue. Health systems must financially commit to an ethical workplace culture that explicitly values mental health and well-being.

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI.

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

"The hierarchy is your constraint:" a qualitative investigation of social workers' moral distress across a U.S. health system.

This paper reports findings from a qualitative study on the triggers of hospital social workers' moral distress at a large southern U.S. health system. Moral distress occurs when ethical conflict cannot be resolved in a way that aligns with an individual's personal and professional values and ethics. Participants indicated that moral distress derives from both individual interactions and the culture and climate of health systems. For example, participants expressed how sources of moral distress derived from client-centered decisions, such as end-of-life care and patient autonomy; interpersonal dynamics, including team or supervisory conflict; structural issues, such as insurance barriers or internal hospital policies; and organizational values, such as perceptions of institutional support and validation. Implications of this research suggest that health systems need to foster positive ethical environments that nurture clinicians' health and mental health through programs that aim to increase moral resilience, promote empowerment, and foster wellness.

Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans.

During haematopoiesis, haematopoietic stem cells differentiate into restricted potential progenitors before maturing into the many lineages required for oxygen transport, wound healing and immune response. We have updated Haemopedia, a database of gene-expression profiles from a broad spectrum of haematopoietic cells, to include RNA-seq gene-expression data from both mice and humans. The Haemopedia RNA-seq data set covers a wide range of lineages and progenitors, with 57 mouse blood cell types (flow sorted populations from healthy mice) and 12 human blood cell types. This data set has been made accessible for exploration and analysis, to researchers and clinicians with limited bioinformatics experience, on our online portal Haemosphere: https://www.haemosphere.org. Haemosphere also includes nine other publicly available high-quality data sets relevant to haematopoiesis. We have added the ability to compare gene expression across data sets and species by curating data sets with shared lineage designations or to view expression gene vs gene, with all plots available for download by the user.

MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors. METHODS: We performed a high-throughput screen of 484 small-molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice. RESULTS: Cells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heat shock protein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of patient-derived organoids to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21. CONCLUSIONS: miRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitors might be developed for the treatment of CCA and miRNA21 might be a marker of sensitivity to these agents.

Unilateral hearing loss in a 94-year-old patient.

A case report of a 94-year-old, previously well male patient who presented with fever thought to be caused by community acquired pneumonia, new unilateral hearing loss and reduced consciousness. Despite antibiotic treatment he continued to deteriorate. Brain imaging with computer tomography and magnetic resonance imaging revealed a left otomastoiditis with osteomyelitis of the skull base, associated with an adjacent subdural empyema. He was also found to have a venous sinus thrombosis, most likely secondary to otitis media. He was managed with intravenous antibiotics, anticoagulation, grommet insertion and a hearing aid and he made a good recovery. This case reminds us to consider otitis media in older patients who present with hearing loss and fever. Otitis media can lead to serious complications including subdural empyema and osteomyelitis of the skull base.

Associations of intestinal helminth infections with health parameters of spring-migrating female lesser scaup (Aythya affinis) in the upper Midwest, USA.

Thousands of lesser scaup (Aythya affinis) die during spring and fall migrations through the upper Midwest, USA, from infections with Cyathocotyle bushiensis and Sphaeridiotrema spp. (Class: Trematoda) after ingesting infected intermediate hosts, such as non-native faucet snails (Bithynia tentaculata). The lesser scaup is a species of conservation concern and is highly susceptible to these infections. We collected female lesser scaup from spring migratory stopover locations throughout Illinois and Wisconsin and assessed biochemical and morphological indicators of health in relation to intestinal helminth loads. Helminth species diversity, total trematode abundance, and the infection intensities of the trematodes C. bushiensis and Sphaeridiotrema spp. were associated with percent body fat, blood metabolites, hematological measures, and an index of foraging habitat quality. Helminth diversity was negatively associated with percent body fat, albumin concentrations, and monocytes, whereas glucose concentrations displayed a slight, positive association. Total trematode abundance was negatively associated with blood concentrations of non-esterified fatty acids and albumin. Infections of C. bushiensis were positively related to basophil levels, whereas Sphaeridiotrema spp. infection intensity was negatively associated with packed cell volume and foraging habitat quality. Thus, commonly measured health metrics may indicate intestinal parasite infections and help waterfowl managers understand overall habitat quality. Intestinal parasitic loads offer another plausible mechanism underlying the spring condition hypothesis.

Environmental controls on canopy foliar nitrogen distributions in a Neotropical lowland forest.

Distributions of foliar nutrients across forest canopies can give insight into their plant functional diversity and improve our understanding of biogeochemical cycling. We used airborne remote sensing and partial least squares regression to quantify canopy foliar nitrogen (foliar N) across ~164 km2 of wet lowland tropical forest in the Osa Peninsula, Costa Rica. We determined the relative influence of climate and topography on the observed patterns of foliar N using a gradient boosting model technique. At a local scale, where climate and substrate were constant, we explored the influence of slope position on foliar N by quantifying foliar N on remnant terraces, their adjacent slopes, and knife-edged ridges. In addition, we climbed and sampled 540 trees and analyzed foliar N in order to quantify the role of species identity (phylogeny) and environmental factors in predicting foliar N. Observed foliar N heterogeneity reflected environmental factors working at multiple spatial scales. Across the larger landscape, elevation and precipitation had the highest relative influence on predicting foliar N (30% and 24%), followed by soils (15%), site exposure (9%), compound topographic index (8%), substrate (6%), and landscape dissection (6%). Phylogeny explained ~75% of the variation in the field collected foliar N data, suggesting that phylogeny largely underpins the response to the environmental factors. Taken together, these data suggest that a large fraction of the variance in foliar N across the landscape is proximately driven by species composition, though ultimately this is likely a response to abiotic factors such as climate and topography. Future work should focus on the mechanisms and feedbacks involved, and how shifts in climate may translate to changes in forest function.

Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

Gnathostoma spinigerum in live Asian swamp eels (Monopterus spp.) from food markets and wild populations, United States.

In Southeast Asia, swamp eels (Synbranchidae: Monopterus spp.) are a common source of human gnathostomiasis, a foodborne zoonosis caused by advanced third-stage larvae (AL3) of Gnathostoma spp. nematodes. Live Asian swamp eels are imported to US ethnic food markets, and wild populations exist in several states. To determine whether these eels are infected, we examined 47 eels from markets and 67 wild-caught specimens. Nematodes were identified by morphologic features and ribosomal intergenic transcribed spacer-2 gene sequencing. Thirteen (27.7%) M. cuchia eels from markets were infected with 36 live G. spinigerum AL3: 21 (58.3%) in liver; 7 (19.4%) in muscle; 5 (13.8%) in gastrointestinal tract, and 3 (8.3%) in kidneys. Three (4.5%) wild-caught M. albus eels were infected with 5 G. turgidum AL3 in muscle, and 1 G. lamothei AL3 was found in a kidney (both North American spp.). Imported live eels are a potential source of human gnathostomiasis in the United States.

Neuregulin-1 potentiates agrin-induced acetylcholine receptor clustering through muscle-specific kinase phosphorylation.

At neuromuscular synapses, neural agrin (n-agrin) stabilizes embryonic postsynaptic acetylcholine receptor (AChR) clusters by signalling through the muscle-specific kinase (MuSK) complex. Live imaging of cultured myotubes showed that the formation and disassembly of primitive AChR clusters is a dynamic and reversible process favoured by n-agrin, and possibly other synaptic signals. Neuregulin-1 is a growth factor that can act through muscle ErbB receptor kinases to enhance synaptic gene transcription. Recent studies suggest that neuregulin-1-ErbB signalling can modulate n-agrin-induced AChR clustering independently of its effects on transcription. Here we report that neuregulin-1 increased the size of developing AChR clusters when injected into muscles of embryonic mice. We investigated this phenomenon using cultured myotubes, and found that in the ongoing presence of n-agrin, neuregulin-1 potentiates AChR clustering by increasing the tyrosine phosphorylation of MuSK. This potentiation could be blocked by inhibiting Shp2, a postsynaptic tyrosine phosphatase known to modulate the activity of MuSK. Our results provide new evidence that neuregulin-1 modulates the signaling activity of MuSK and hence might function as a second-order regulator of postsynaptic AChR clustering at the neuromuscular synapse. Thus two classic synaptic signalling systems (neuregulin-1 and n-agrin) converge upon MuSK to regulate postsynaptic differentiation.

Confronting moral injury across health systems: Enhancing medical social workers' resilience and well-being.

Research has demonstrated that encounters of potentially moral injurious events (PMIEs) may result in longstanding psychological trauma that impact healthcare workers' mental health and well-being. In this paper, we explore strategies to alleviate PMIEs for medical social workers. In-depth semi-structured interviews (30-60 min) were conducted with medical social workers (n = 75) across the state of Texas. Supported by directed content analysis, textual data were coded and categorised to finalize emerging themes. Findings demonstrate that multilevel strategies ought to be implemented into daily healthcare practice. PMIEs that impact frontline healthcare delivery can be alleviated by having formal and informal support systems (e.g., mentorship, supervision, counselling) as well as honest and transparent interprofessional collaborative care to facilitate psychological team safety. PMIEs across the healthcare organisation, perhaps due to internal policies and practices, may be reduced by implementing educational initiatives and building ethical workplace cultures that serve to explicitly reduce stigma associated with mental health and enhance worker well-being. PMIEs that derive from macro-level social policies (e.g., insurance, health disparities) may be alleviated by instituting patient advocacy initiatives and dismantling systems of oppression to lessen psychological stress and trauma. Hospital leadership ought to understand how the United States healthcare industry triggers PMIEs across the healthcare workforce. Multi-tiered practices and policies that addresses frontline delivery care, leadership and administrative responsibilities, and the healthcare industry can enhance psychologically safe workplaces and elicit macro-level institutional reform in how health systems function. These findings have important implications for healthcare policy makers, practitioners, educators, and researchers to inform future research and practice development.

Opioid modulation of prefrontal cortex cells and circuits.

Several neurochemical systems converge in the prefrontal cortex (PFC) to regulate cognitive and motivated behaviors. A rich network of endogenous opioid peptides and receptors spans multiple PFC cell types and circuits, and this extensive opioid system has emerged as a key substrate underlying reward, motivation, affective behaviors, and adaptations to stress. Here, we review the current evidence for dysregulated cortical opioid signaling in the pathogenesis of psychiatric disorders. We begin by providing an introduction to the basic anatomy and function of the cortical opioid system, followed by a discussion of endogenous and exogenous opioid modulation of PFC function at the behavioral, cellular, and synaptic level. Finally, we highlight the therapeutic potential of endogenous opioid targets in the treatment of psychiatric disorders, synthesizing clinical reports of altered opioid peptide and receptor expression and activity in human patients and summarizing new developments in opioid-based medications. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Morbidity in California giant salamander (Dicamptodon ensatus Eschscholtz, 1833) caused by Euryhelmis sp. Poche, 1926 (Trematoda: Heterophyiidae).

In the fall of 2021, California Department of Fish and Wildlife reported larval and adult California giant salamanders (Dicamptodon ensatus Eschscholtz, 1833) with skin lesions at multiple creeks in Santa Clara and Santa Cruz Counties, California, USA. Field signs in both stages included rough, lumpy textured skin, and larvae with tails that were disproportionately long, flat, wavy, and flaccid. Presence of large-bodied larvae suggested delayed metamorphosis, with some larvae having cloudy eyes and suspected blindness. To determine the cause of the disease, three first-of-the-year salamanders from one location were collected, euthanized with 20% benzocaine, and submitted for necropsy to the U.S. Geological Survey, National Wildlife Health Center. Upon gross examination, all salamanders were emaciated with no internal fat stores, and had multiple pinpoint to 1.5-mm diameter raised nodules in the skin over the body, including the head, gills, dorsum, ventrum, all four limbs, and the tail; one also had nodules in the oral cavity and tongue. Histologically all salamanders had multiple encysted metacercariae in the dermis, subcutis, and skeletal muscles of the head, body, and tail that were often associated with granulomatous and granulocytic inflammation and edema. A small number of encysted metacercariae or empty cysts were present in the gills with minimal inflammation, and rarely in the kidney with no associated inflammation. Morphology of live metacercariae (Trematoda: Heterophyiidae), and sequencing of the 28S rRNA gene identified a species of Euryhelmis (Poche, 1926). Artificial digestion of a 1.65 g, decapitated, eviscerated carcass yielded 773 metacercariae, all of similar size and morphology as the live specimens. Based on these findings, the poor body condition of these salamanders was concluded to be due to heavy parasite burden. Environmental factors such as drought, increased temperature, and overcrowded conditions may be exacerbating parasite infections in these populations of salamander.

Parvalbumin interneuron mGlu5 receptors govern sex differences in prefrontal cortex physiology and binge drinking.

Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. Activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu1 and mGlu5 metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5 receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5-/- mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol's stimulant properties. Importantly, these studies identify mGlu1 and mGlu5 receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant for alcohol use.

Lessons learned from using wild-caught and captive-reared lesser scaup (Aythya affinis) in captive experiments.

Waterfowl are housed in captivity for research studies that are infeasible in the wild. Accommodating the unique requirements of semi-aquatic species in captivity while meeting experimental design criteria for research questions can be challenging and may have unknown effects on animal health. Thus, testing and standardizing best husbandry and care practices for waterfowl is necessary to facilitate proper husbandry and humane care while ensuring reliable and repeatable research results. To inform husbandry practices for captive-reared and wild-caught lesser scaup (Aythya affinis; hereafter, scaup), we assessed body mass and fat composition across two different aspects of husbandry, source population (captive-reared or wild caught), and housing densities (birds/m2). Our results suggest that housing scaup at low densities (≤0.6 m2/bird, P = 0.049) relative to other species can minimize negative health effects. Captive-reared scaup were heavier (P = 0.027) with greater body fat (P < 0.001) and exhibited fewer signs of stress during handling than wild-caught scaup. In our experience, scaup which are captive-reared from eggs collected in the wild were better for long-term captivity studies as they maintained body mass between and recovered lost body mass following trials. Researchers would benefit from carefully evaluating the tradeoffs of using short- and long-term captive methods on their research question before designing projects, husbandry practices, and housing facilities for waterfowl.