We examined the content of tweets on the social media site Twitter to better understand the contemporary discourse about medications for opioid use disorder (MOUD), how this chat contributes to the pervasive underpinnings of drug addiction, chronic pain stigma, and the impact it has on demand and availability of treatment. A retrospective review of tweets over 3 months containing keywords buprenorphine, naltrexone, methadone, or bupe was conducted resulting in 5,068 tweets. A content analysis was carried out focusing on a subset of tweets. Themes emerged from including suspicion and conspiracy theories about MOUD, and frustration and lack of control over their treatment options. Other tweets shared stigmatizing language and attitudes related to OUD/MOUD (e.g., “Junkies”). Twitter is a rich source of data reflecting thoughts, opinions, and sentiments entities regarding MOUD. However, this information can contain malicious comments that perpetuate stigma for people with OUD and result in avoidance of treatment.

Bushy neurons of the cochlear nucleus encode temporal fine structure and modulation of sound with high fidelity. However, the synaptic maps and electrotonic structures that underlie these properties are not specified in meaningful explanatory detail. We employed modern volume electron microscopy techniques to provide exact data on the numbers of synaptic inputs and their weights determined by the number of contained active zones, and the surface areas of all postsynaptic cellular compartments. Leveraging these high-resolution images, we discovered cabling of dendrite branches and new structures within dendrites, and identified non-innervated dendrites. We extend current nanoscale connectomic studies with methods to export cellular reconstructions into morphologically-constrained, biophysically-based predictive computational models. We reveal both coincidence detection and mixed supra/subthreshold modes of input convergence across the bushy cell population and show subthreshold inputs contribute to enhanced temporal encoding even in the presence of suprathreshold inputs. We demonstrate the variation of dendritic load and axon parameters and their importance in controlling excitability as potential homeostatic mechanisms, thereby defining heterogeneity in stimulus-evoked responses across the BC population.

BACKGROUND Diffuse midline glioma (DMG), H3K27-altered, is a rare, highly malignant central nervous system neoplasm that arises in midline structures. They are more commonly encountered in children and are rarely encountered in adults, usually in the thalamus or spinal cord. The presence of the H3K27 mutation in the H3F3A gene automatically classifies a tumor as World Health Organization grade IV. These tumors carry a grim prognosis, with an overall median survival of less than 1 year. OBSERVATIONS The authors report the case of a 38-year-old male presenting with acute-onset urinary retention who was found to have an expansile, well-circumscribed mass involving the conus medullaris at the level of T12–L1. A T12–L1 laminectomy and tumor debulking were performed. Pathology revealed glial cells with astrocytic morphology among Rosenthal fibers, microvascular proliferation, and cellular atypia. The H3K27 mutation was confirmed. LESSONS DMG, H3K27-altered, is a rarely encountered entity that can present in numerous midline structures. If localized to the conus medullaris, it may present as acute-onset urinary retention in a previously asymptomatic patient. Further investigation is needed to characterize its molecular and clinical features in adults to improve the management of those presenting with these tumors.

Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory- nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically-based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically-detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes.

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