Cholinergic Neuronal Activity Promotes Diffuse Midline Glioma Growth through Muscarinic Signaling.

Neuronal activity promotes the proliferation of healthy oligodendrocyte precursor cells (OPC) and their malignant counterparts, gliomas. Many gliomas arise from and closely resemble oligodendroglial lineage precursors, including diffuse midline glioma (DMG), a cancer affecting midline structures such as the thalamus, brainstem and spinal cord. In DMG, glutamatergic and GABAergic neuronal activity promotes progression through both paracrine signaling and through bona-fide neuron-to-glioma synapses.

Myelin plasticity in the ventral tegmental area is required for opioid reward.

All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance-use disorders. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behaviour. Here we explore the role of myelin plasticity in dopaminergic circuitry and reward learning.

Immunotherapy-related cognitive impairment after CAR T cell therapy in mice.

Persistent central nervous system (CNS) immune dysregulation and consequent dysfunction of multiple neural cell types is central to the neurobiological underpinnings of a cognitive impairment syndrome that can occur following traditional cancer therapies or certain infections. Immunotherapies have revolutionized cancer care for many tumor types, but the potential long-term cognitive sequelae are incompletely understood. Here, we demonstrate in mouse models that chimeric antigen receptor (CAR) T cell therapy for both CNS and non-CNS cancers can impair cognitive function and induce a persistent CNS immune response characterized by white matter microglial reactivity and elevated cerebrospinal fluid (CSF) cytokines and chemokines.

Training the next generation of community-engaged physicians: a mixed-methods evaluation of a novel course for medical service learning in the COVID-19 era.

Background: Medical school curricula strive to train community-engaged and culturally competent physicians, and many use service learning to instill these values in students. The current standards for medical service learning frameworks have opportunities for improvement, such as encouraging students to have more sustainable and reciprocal impact and to ingrain service learning as a value to carry throughout their careers rather than a one-time experience. PEDS 220: A COVID-19 Elective is a Stanford University course on the frontlines of this shift; it provides timely education on the COVID-19 pandemic, integrating community-oriented public health work to help mitigate its impact.

The logic of recurrent circuits in the primary visual cortex.

Recurrent cortical activity sculpts visual perception by refining, amplifying or suppressing visual input. However, the rules that govern the influence of recurrent activity remain enigmatic. We used ensemble-specific two-photon optogenetics in the mouse visual cortex to isolate the impact of recurrent activity from external visual input.

Glioma synapses recruit mechanisms of adaptive plasticity.

The role of the nervous system in the regulation of cancer is increasingly appreciated. In gliomas, neuronal activity drives tumour progression through paracrine signalling factors such as neuroligin-3 and brain-derived neurotrophic factor (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. The consequent glioma cell membrane depolarization drives tumour proliferation.

Tumors on different wavelengths.

Brain metastases cause cognitive impairment and impair quality of life. Sanchez-Aguilera et al. examine the effects of metastases on brain function leveraging in vivo electrocorticography and machine learning to reveal tumor model-specific changes in neural circuit dynamics and find that the electrophysiological profile predicts the presence and type of brain metastasis.

Glioblastoma remodelling of human neural circuits decreases survival.

Gliomas synaptically integrate into neural circuits. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth and gliomas increasing neuronal excitability. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival.

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11.

Applying Kern's Six Steps to the Development of a Community-Engaged, Just-in-Time, Interdisciplinary COVID-19 Curriculum.

Universities and medical schools often work towards operationalizing their shared mission of facilitating community-engaged work independently. Based on their experience teaching the COVID-19 Elective course at Stanford University School of Medicine, the authors proposed a novel solution for universities and medical schools to achieve an interdisciplinary collaboration within a diverse student population by creating targeted, project-based, and community-engaged courses for addressing emergent health needs. In this article, the authors discuss their curriculum, which was created using Kern's six-step approach for curriculum development, to address emergent health needs related to the novel coronavirus pandemic.

A silicon-rhodamine chemical-genetic hybrid for far red voltage imaging from defined neurons in brain slice.

We describe the design, synthesis, and application of voltage-sensitive silicon rhodamines. Based on the Berkeley Red Sensor of Transmembrane potential, or BeRST, scaffold, the new dyes possess an isomeric molecular wire for improved alignment in the plasma membrane and 2' carboxylic acids for ready functionalization. The new isoBeRST dyes have a voltage sensitivity of 24% Δ/ per 100 mV.

Covalently Tethered Rhodamine Voltage Reporters for High Speed Functional Imaging in Brain Tissue.

Voltage-sensitive fluorophores enable the direct visualization of membrane potential changes in living systems. To pair the speed and sensitivity of chemically synthesized fluorescent indicators with cell-type specific genetic methods, we here develop Rhodamine-based Voltage Reporters (RhoVR) that can be covalently tethered to genetically encoded, self-labeling enzymes. These chemical-genetic hybrids feature a photoinduced electron transfer triggered RhoVR voltage-sensitive indicator coupled to a chloroalkane HaloTag ligand through a long, water-soluble polyethylene glycol linker (RhoVR-Halo).

A Map of Toll-like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type-Specific, and Temporal Patterns.

Signaling by Toll-like receptors (TLRs) on intestinal epithelial cells (IECs) is critical for intestinal homeostasis. To visualize epithelial expression of individual TLRs in vivo, we generated five strains of reporter mice. These mice revealed that TLR expression varied dramatically along the length of the intestine.

A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex.

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map.