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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.

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.

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.

Psychedelics induce fast and long-lasting antidepressant effects and neuronal plasticity, but their hallucinogenic effects limit their use. We show that, in mice, psychedelics bind directly to TrkB (the brain-derived neurotrophic factor (BDNF) receptor) with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.

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.

Moliner et al. show that psychedelics directly bind to the BDNF receptor TrkB with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.

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.

A study by Holstein-Rønsbo, Gan et al. published in this issue of Nature Neuroscience adds another dimension to the ‘glymphatic’ story — the role of functional hyperemia facilitating perivascular flow of cerebrospinal fluid along pial arteries.

Sleep helps to stabilize long-term memories, possibly through the temporal synchronization of neuronal activity in different brain regions. Intracranial stimulation during sleep using prefrontal electric pulses, precisely timed with slow-wave activities in the medial temporal lobe, enhanced the coupling of neuronal oscillations across regions of the human brain and improved memory performance.

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.

Geva-Sagiv et al. performed real-time closed-loop intracranial stimulation in human sleep. Brief prefrontal pulses, precisely timed with MTL slow-wave active periods, led to correlated enhancements in sleep oscillation coupling and memory accuracy.

Holstein-Rønsbo et al. show that functional hyperemia increases glymphatic CSF inflow and clearance. Direct stimulation of vascular smooth muscle cells, in the absence of neuronal activation, similarly enhances glymphatic flow.

Sun et al. analyzed 22,514 human brain vascular single-nucleus transcriptomes from 428 individuals and uncovered AD-related gene expression and cell–cell interaction linked to genetics, as well as vascular dysfunction in APOE-associated cognitive decline.

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.

Hahamy et al. demonstrate that, at the transitions between narrative events, the human brain reactivates past information that is relevant for the understanding of the current narrative stage.

Reconstitution of TDP-43 filaments that exhibit sequence and morphological features similar to those found in the brain helps to uncover a new mechanism for the formation and propagation of pathology in amyotrophic lateral sclerosis and other neurodegenerative diseases.