A Thalamic Orphan Receptor Drives Variability in Short-Term Memory.

Working memory is a form of short-term memory that involves maintaining and updating task-relevant information toward goal-directed pursuits. Classical models posit persistent activity in prefrontal cortex (PFC) as a primary neural correlate, but emerging views suggest additional mechanisms may exist. We screened ∼200 genetically diverse mice on a working memory task and identified a genetic locus on chromosome 5 that contributes to a substantial proportion (17%) of the phenotypic variance. Within the locus, we identified a gene encoding an orphan G-protein-coupled receptor, Gpr12, which is sufficient to drive substantial and bidirectional changes in working memory. Molecular, cellular, and imaging studies revealed that Gpr12 enables high thalamus-PFC synchrony to support memory maintenance and choice accuracy. These findings identify an orphan receptor as a potent modifier of short-term memory and supplement classical PFC-based models with an emerging thalamus-centric framework for the mechanistic understanding of working memory.

Prefrontal feature representations drive memory recall.

Memory formation involves binding of contextual features into a unitary representation1-4, whereas memory recall can occur using partial combinations of these contextual features. The neural basis underlying the relationship between a contextual memory and its constituent features is not well understood; in particular, where features are represented in the brain and how they drive recall. Here, to gain insight into this question, we developed a behavioural task in which mice use features to recall an associated contextual memory. We performed longitudinal imaging in hippocampus as mice performed this task and identified robust representations of global context but not of individual features. To identify putative brain regions that provide feature inputs to hippocampus, we inhibited cortical afferents while imaging hippocampus during behaviour. We found that whereas inhibition of entorhinal cortex led to broad silencing of hippocampus, inhibition of prefrontal anterior cingulate led to a highly specific silencing of context neurons and deficits in feature-based recall. We next developed a preparation for simultaneous imaging of anterior cingulate and hippocampus during behaviour, which revealed robust population-level representation of features in anterior cingulate, that lag hippocampus context representations during training but dynamically reorganize to lead and target recruitment of context ensembles in hippocampus during recall. Together, we provide the first mechanistic insights into where contextual features are represented in the brain, how they emerge, and how they access long-range episodic representations to drive memory recall.

Bridging the Gap: Impact of dedicated post-discharge services on readmission rates and emergency department visits for psychiatrically hospitalized youth.

BACKGROUND: For psychiatrically hospitalized youth, discharge care coordination can reduce suicide risk and rehospitalization, but studies on effective interventions or programs are sparse. This study aimed to examine the impact of a dedicated post-discharge bridging service including case management and therapeutic supports on readmissions and emergency department presentations. METHODS: This retrospective cohort study compared emergency department mental health visits (EDMH) and psychiatric hospitalizations in the 60 days before the hospitalization which included referral to the bridging service, and in the 60 days post-hospitalization. RESULTS: This diagnostically heterogeneous group of 238 youth had a mean age of 14 years and were of similar racial and ethnic background as the broader inpatient population. There was a nominal decrease in hospitalizations (p = 0.251), and a significant decrease in EDMH (p < 0.001) in the 60 days following referral to this program compared to the 60 days prior. Further, the proportion of patients with at least one EDMH or hospitalization decreased significantly before and after linkage with this service from 42.4% to 27.3% (p < 0.001). CONCLUSION: Dedicated post-discharge bridging services including family-centered, flexible case management and therapeutic supports can reduce EDMH visits and potentially lower readmission for children and adolescents.

Building a Networked Improvement Community: Lessons in Organizing to Promote Diversity, Equity, and Inclusion in Science, Technology, Engineering, and Mathematics.

In 2016, 10 universities launched a Networked Improvement Community (NIC) aimed at increasing the number of scholars from Alliances for Graduate Education and the Professoriate (AGEP) populations entering science, technology, engineering, and mathematics (STEM) faculty careers. NICs bring together stakeholders focused on a common goal to accelerate innovation through structured, ongoing intervention development, implementation, and refinement. We theorized a NIC organizational structure would aid understandings of a complex problem in different contexts and accelerate opportunities to develop and improve interventions to address the problem. A distinctive feature of this NIC is its diverse institutional composition of public and private, predominantly white institutions, a historically Black university, a Hispanic-serving institution, and land grant institutions located across eight states and Washington, DC, United States. NIC members hold different positions within their institutions and have access to varied levers of change. Among the many lessons learned through this community case study, analyzing and addressing failed strategies is as equally important to a healthy NIC as is sharing learning from successful interventions. We initially relied on pre-existing relationships and assumptions about how we would work together, rather than making explicit how the NIC would develop, establish norms, understand common processes, and manage changing relationships. We had varied understandings of the depth of campus differences, sometimes resulting in frustrations about the disparate progress on goals. NIC structures require significant engagement with the group, often more intensive than traditional multi-institution organizational structures. They require time to develop and ongoing maintenance in order to advance the work. We continue to reevaluate our model for leadership, climate, diversity, conflict resolution, engagement, decision-making, roles, and data, leading to increased investment in the success of all NIC institutions. Our NIC has evolved from the traditional NIC model to become the Center for the Integration of Research, Teaching and Learning (CIRTL) AGEP NIC model with five key characteristics: (1) A well-specified aim, (2) An understanding of systems, including a variety of contexts and different organizations, (3) A culture and practice of shared leadership and inclusivity, (4) The use of data reflecting different institutional contexts, and (5) The ability to accelerate infrastructure and interventions. We conclude with recommendations for those considering developing a NIC to promote diversity, equity, and inclusion efforts.

Effects of Bariatric Surgery Observed in Postmortem Toxicology Casework.

Bariatric surgery has been on the rise and patients often have multiple indications for pre- and post-operative pharmacotherapy. Procedures target the stomach and/or small intestine and affect weight loss through restriction, malabsorption, or a combination of the two. The absorption and/or metabolism of drugs via the gastrointestinal tract could be altered by different mechanisms. Several cases at the North Carolina Office of the Chief Medical Examiner's Toxicology Laboratory (NCOCME) have raised questions about the potential impact of these procedures on the disposition of drugs in the body and how that altered disposition may affect cause and manner of death. Overmedication and postmortem redistribution are not enough to explain the phenomena seen in some NCOCME bariatric surgery-related casework. Case examples include a 46-year-old female with a history of Roux-en-Y gastric bypass (RYGB) who suffered a witnessed collapse. Toxicological findings included elevated concentrations of oxymorphone at 0.49 mg/L in vena cava blood. A 67-year-old female, who died from vomiting and bacterial gastritis one day after placement of two intragastric weight-loss balloons, had elevated concentrations of duloxetine at 1.4 mg/L in the iliac vein blood and 9.3 mg/kg in the liver. Her medication was strictly controlled by her sister and gastric contents were without intact tablets or residue at autopsy.