Volume 26 Issue 7, July 2023

Neuroscience research is affected by a substantial racial bias, but there are major challenges involved in minimizing this bias. Here we discuss these challenges and call for a global discussion that develops answers to these challenges and defines best practices for how researchers can better represent human diversity and work against medical racism. This global discussion should involve researchers from medicine, life sciences, social sciences, and humanities, as well as people with lived experience and health equity activists, to improve racial and ethnic equity in neuroscience research and beyond.

As Nature Neuroscience celebrates its 25th anniversary, we are having conversations with both established leaders in the field and those earlier in their careers to discuss how the field has evolved and where it is heading. This month we are talking to Carla Shatz, who is the Sapp Family Provostial Professor, Catherine Holman Johnson Director of Stanford Bio-X, and Professor of Biology and Neurobiology at Stanford University. Her work has illuminated mechanisms of visual system development and plasticity and has focused more recently on synaptic pruning mechanisms.

Vasek et al. show that microglia perform protein translation in their processes and that this translation is important for the number of processes and formation of phagocytic cups. These findings may provide insight into how microglia respond rapidly to a wide variety of local signals in defined cellular compartments.

β2-Microglobulin (β₂M) is an amyloidogenic protein. β₂M coaggregates with β-amyloid (Aβ) in the brains of patients with Alzheimer’s disease and enhances Aβ deposition. β₂M is essential for Aβ neurotoxicity in vivo, and neutralization of pathogenetic β₂M–Aβ aggregates ameliorates the amyloid pathology and cognitive deficits associated with disease in a mouse model.

By studying axonal pathology in human multiple sclerosis and its models, we observed that myelin ensheathment itself can be detrimental for axonal survival. We hypothesize that oligodendroglial support is disrupted under inflammatory conditions, with the most severe consequences for the axons that remain physically isolated from the extracellular milieu by myelin.

This Review provides a comprehensive overview of the neuronal heterogeneity, circuit architecture and functional roles of the external globus pallidus, with emphasis on how the latest data deviate from traditional views of the basal ganglia.

The biological meaning of eye pupil size is a subject of intense research. This study shows that pupil fluctuations reveal information about hypothalamic orexin cells, which control pupil size via a noradrenaline neural circuit.

Using depth electrodes in human patients, scientists at the Mayo Clinic found that the map of the body in motor cortex extends deep into the central sulcus. Unexpectedly, the nonsomatotopic ‘Rolandic motor association’ (RMA) area interrupts this organization.

Zhao et al. identified β₂-microglobulin (β₂M) as an essential factor driving β-amyloid (Aβ) neurotoxicity and cognitive impairment in mouse models of Alzheimer’s disease (AD) and implicated targeting β₂M–Aβ coaggregation as a strategy for AD therapeutics.

Vasek et al. demonstrate that distal processes of microglia locally translate specific mRNAs including those related to immunity and phagocytosis. They then show that local protein synthesis is necessary for microglial process-initiated phagocytosis.

Yin et al. identify miR-155–IFN-γ signaling that regulates a protective microglial subset in a mouse model of Alzheimer’s disease. These microglia enhance plaque compaction, reduce dystrophic neurites and synaptic degradation, and improve cognition.

Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.

Myelin is widely believed to protect axons from damage in multiple sclerosis. The authors challenge this view and find that myelin insulation renders axons more vulnerable to degeneration in an autoimmune environment.

Oxycodone withdrawal triggered distinct transcriptomic changes in the ventral tegmental area, nucleus accumbens and medial prefrontal cortex in mice with and without chronic pain, with histone deacetylase 1 (HDAC1) as a common upstream regulator. A novel HDAC1/HDAC2 inhibitor reduced behavioral manifestations of oxycodone withdrawal.

The authors find a surprising diversity in hypothalamic neurons projecting to habenula, and using patch-sequencing (Patch-seq), identify an estrogen receptor-expressing neuron type that signals aversion and is linked to stress in female mice.

Camacho et al. show that emotion concepts are represented throughout the brain, giving insight to how the brain perceives real-world emotions. These patterns are present before children enter school and become more standardized across adolescence.

By inferring the cellular landscape of the neocortex in 638 aged individuals from RNA profiles, the authors uncovered unique cellular communities composed of coordinated populations of multiple cell types, which were altered in Alzheimer’s disease.

Froudist-Walsh et al. reveal organizational principles of receptor densities in macaque cortex. Densities of multiple receptor types align with changes in dendritic properties, myelin and functional networks. Data are openly released to the community.

Bonheur et al. developed a subcellular-distribution-based bidirectional neural activity reporter that operates on the timescale of minutes, and they demonstrate increases and decreases of neural activity associated with social behaviors in Drosophila.