A Student Teaching Assistant Program for Diversity, Equity, Inclusion, and Antiracism Curricular Enhancement.

PROBLEM: In the United States, physician bias is exhibited early in medical training and contributes to systemic inequities within the field of medicine. A lack of diversity, equity, inclusion, and antiracism (DEI-AR) content within medical curricula drives critical gaps in knowledge and deficiencies when preparing medical students to serve patients of diverse backgrounds. At the Mayo Clinic Alix School of Medicine (MCASOM), student-led curricular reviews between 2017 to 2018 and 2020 to 2021 revealed opportunities to improve DEI-AR content within preclinical courses. Course directors expressed concern of limited expertise and time to enact effective changes. APPROACH: The MCASOM DEI-AR teaching assistant (TA) program aims to curate a collaborative partnership between course directors and compensated student TAs to facilitate course enhancements responsive to the prior preclinical course review while centering standardized DEI-AR best practices. OUTCOMES: As of January 2024, the program has engaged 14 TAs and partnered with 24 preclinical courses. Postcourse student evaluation responses were collected from 8 courses for 2021 to 2022 (before enhancements) and 2022 to 2023 (after enhancements). Student satisfaction with DEI-AR content is tracked through postcourse evaluations, with preliminary data demonstrating improvement after DEI-AR curricular integration (improvement of mean preenhancement and postenhancement scores of 3.81 to 4.05; t12 = 1.79, P = .21). Qualitative student comments were sorted into general categories of positive, negative, or neutral, showing a 6.25% median increase in positive perception of DEI. NEXT STEPS: Plans for the MCASOM DEI-AR TA program include application of quality improvement strategies to improve program processes and outcomes. Development of a centralized dashboard that integrates course enhancement progress and ongoing feedback from evaluations is anticipated to facilitate this effort. The program additionally aims to develop partnerships with clinical clerkships, which would allow for a more comprehensive enhancement of the overall medical education experience related to DEI-AR.

NOise Reduction with DIstribution Corrected (NORDIC) PCA improves signal-to-noise in rodent resting-state and optogenetic functional MRI.

NOise Reduction with DIstribution Corrected (NORDIC) principal component analysis (PCA) has been shown to selectively suppress thermal noise and improve temporal signal-to-noise ratio (tSNR) in human functional magnetic resonance imaging (fMRI). However, the feasibility to improve rodent fMRI using NORDIC PCA has not been explored. In this study, we developed a rodent fMRI preprocessing pipeline by incorporating NORDIC and evaluated its performance in a range of rodent fMRI applications from resting-state fMRI to task-evoked fMRI using optogenetics. In resting-state fMRI, we demonstrated a significant increase in tSNR by more than 3 times after NORDIC correction with reduced variance and improved task-free relative cerebrovascular reactivity (rCVR) across cortical depth. In optogenetic fMRI, apart from tSNR increase, more activated voxels and a significant decrease in the variance of activated brain signals were observed after NORDIC correction without apparent change in brain morphology. Taken together, our results signified the values of NORDIC correction for better detection of brain activities in rodent fMRI. Clinical Relevance: NORDIC PCA increases temporal signalto- noise ratio in rodent resting-state and task-evoked functional MRI, which can play an important role in improving the image quality for translational medicine and preclinical research, and for guiding future clinical neuroimaging.

The kappa opioid receptor modulates GABA neuron excitability and synaptic transmission in midbrainprojections from the insular cortex.

As an integrative hub, the insular cortex (IC) translates external cues into interoceptive states that generate complex physiological, affective, and behavioral responses. However, the precise circuit and signaling mechanisms in the IC that modulate these processes are unknown. Here, we describe a midbrain-projecting microcircuit in the medial aspect of the agranular IC that signals through the Gαi/o-coupled kappa opioid receptor (KOR) and its endogenous ligand dynorphin (Dyn). Within this microcircuit, Dyn is robustly expressed in layer 2/3, while KOR is localized to deep layer 5, which sends a long-range projection to the substantia nigra (SN). Using ex vivo electrophysiology, we evaluated the functional impact of KOR signaling in layer 5 of the IC. We found that bath application of dynorphin decreased GABA release and increased glutamate release on IC-SN neurons, but did not alter their excitability. Conversely, dynorphin decreased the excitability of GABA neurons without altering synaptic transmission. Pretreatment with the KOR antagonist nor-BNI blocked the effects of dynorphin in IC-SN neurons and GABA neurons, indicating that the changes in synaptic transmission and excitability were selectively mediated through KOR. Selective inhibition of IC GABA neurons using a KOR-derived DREADD recapitulated these effects. This work provides insight into IC microcircuitry and indicates that Dyn/KOR signaling may act to directly reduce activity of layer 5 GABA neurons. In turn, KOR-driven inhibition of GABA promotes disinhibition of IC-SN neurons, which can modulate downstream circuits. Our findings present a potential mechanism whereby chronic upregulation of IC Dyn/KOR signaling can lead to altered subcortical function and downstream activity.