Neural mechanism of acute stress regulation by trace aminergic signalling in the lateral habenula in male mice.

Stress management is necessary for vertebrate survival. Chronic stress drives depression by excitation of the lateral habenula (LHb), which silences dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neuronal projection from the rostromedial tegmental nucleus (RMTg). However, the effect of acute stress on this LHb-RMTg-VTA pathway is not clearly understood. Here, we used fluorescent in situ hybridisation and in vivo electrophysiology in mice to show that LHb aromatic L-amino acid decarboxylase-expressing neurons (D-neurons) are activated by acute stressors and suppress RMTg GABAergic neurons via trace aminergic signalling, thus activating VTA dopaminergic neurons. We show that the LHb regulates RMTg GABAergic neurons biphasically under acute stress. This study, carried out on male mice, has elucidated a molecular mechanism in the efferent LHb-RMTg-VTA pathway whereby trace aminergic signalling enables the brain to manage acute stress by preventing the hypoactivity of VTA dopaminergic neurons.

Postmortem gene expression profiles in the habenulae of suicides: implication of endothelial dysfunction in the neurovascular system.

The habenula (Hb) is an epithalamic structure that links multiple forebrain areas with the mid/hindbrain monoaminergic systems. As an anti-reward center, it has been implicated in the etiology of various neuropsychiatric disorders, particularly those associated with dysregulated reward circuitry. In this regard, Hb has been proposed as a therapeutic target for treatment-resistant depression associated with a higher risk of suicide. Therefore, we aimed to gain insight into the molecular signatures of the Hb in association with suicide in individuals with major depression. Postmortem gene expression analysis identified 251 differentially expressed genes (DEGs) in the Hb tissue of suicides in comparison with Hb tissues from neurotypical individuals. Subsequent bioinformatic analyses using single-cell transcriptome data from the mouse Hb showed that the levels of a subset of endothelial cell-enriched genes encoding cell-cell junctional complex and plasma membrane-associated proteins, as well as the levels of their putative upstream transcriptional regulators, were significantly affected in suicides. Although our findings are based on a limited number of samples, the present study suggests a potential association of endothelial dysfunction in the Hb with depression and suicidal behavior.

Gene Expression Profiling of the Habenula in Rats Exposed to Chronic Restraint Stress.

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

Lessons from Cadaver Dissection during the COVID-19 Pandemic.

The rapid increase of the coronavirus disease 2019 pandemic from mid-February 2020 has led the anatomy department of the Korea University College of Medicine to cease the dissection laboratory. However, the hands-on anatomy laboratory experience is paramount to maximizing learning outcomes. In this paper, we share the experiences and lessons learned through the face-to-face cadaveric dissection experience during this disruptive situation. To minimize infection risks, the following strategies were applied: first, students' on-campus attendance was reduced; second, body temperatures and symptoms were checked before entering the laboratory, and personal protective equipment was provided to all participants; and third, a negative pressure air circulation system was used in the dissection room. We suggest that conducting face-to-face cadaveric anatomy dissection is feasible when the daily count of newly infected cases stabilizes, and there is ample provision of safety measures to facilitate hands-on education.

Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior.

Calcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive symptoms and the role of CAPS2 remains unclear. We hypothesized that dysfunction of MHb CAPS neurons might cause defects in neuropeptide secretion and the activity of monoaminergic centers, resulting in depressive-like behaviors. In this study, we examined (1) CAPS2 expression in the habenula of depression animal models and major depressive disorder patients and (2) the effects of down-regulation of MHb CAPS2 on the animal behaviors, synaptic transmission in the interpeduncular nucleus (IPN), and neuronal activity of monoamine centers. Habenular CAPS2 expression was decreased in the rat chronic restraint stress model, mouse learned helplessness model, and showed tendency to decrease in depression patients who died by suicide. Knockdown of CAPS2 in the mouse habenula evoked despair-like behavior and a reduction of the release of DCVs in the IPN. Neuronal activity of IPN and monoaminergic centers was also reduced. These results implicate MHb CAPS2 as playing a pivotal role in depressive behavior through the regulation of neuropeptide secretion of the MHb-IPN pathway and the activity of monoaminergic centers.

Adaptations in Anatomy Education during COVID-19.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) has profoundly affected education, with most universities changing face-to-face classes to online formats. To adapt to the COVID-19 pandemic situation, we adopted a blended learning approach to anatomy instruction that included online lectures, pre-recorded laboratory dissection videos, and 3D anatomy applications, with condensed offline cadaver dissection. METHODS: We aimed to examine the learning outcomes of a newly adopted anatomy educational approach by 1) comparing academic achievement between the blended learning group (the 2020 class, 108 students) and the traditional classroom learning group (the 2019 class, 104 students), and 2) an online questionnaire survey on student preference on the learning method and reasons of preference. RESULTS: The average anatomy examination scores of the 2020 class, who took online lectures and blended dissection laboratories, were significantly higher than those of the 2019 class, who participated in an offline lecture and dissection laboratories. The questionnaire survey revealed that students preferred online lectures over traditional large group lecture-based teaching because it allowed them to acquire increased self-study time, study according to their individual learning styles, and repeatedly review lecture videos. CONCLUSION: This study suggests that a blended learning approach is an effective method for anatomy learning, and the advantage may result from increased self-directed study through online learning.