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The Li lab mapped molecularly distinct Purkinje cell (PC) subtypes in 3D and linked them to adult cerebellar architecture. They found that Foxp1/Foxp2 are essential for PC diversity and that Foxp1⁺ PCs are required for the formation of the cerebellar hemisphere.

The embryonic motor neuron selector transcription factors ISL1 and LHX3 can be used to partially rejuvenate the gene expression profile of mature neurons. This process makes neurons more resistant to diseases of aging without compromising their normal function.

In this issue, Stamenkovic et al. describe deep in vivo imaging of the brain vasculature to document its evolution during aging, which identifies a unique vulnerability at the site of convergence of capillaries toward major veins. They propose that pericyte and capillary instability there cause mild hypoperfusion, ultimately leading to myelin degradation.

Human-specialized features of immature dentate granule cells (imGCs) formed during adult hippocampal neurogenesis are poorly characterized. Using machine learning-augmented analysis of single-cell RNA-sequencing data, we have revealed human-specific gene expression but convergent biological processes for imGCs across mammalian species. We further demonstrated functional roles of human imGC-enriched proton-transporting ATPase subtypes in neuronal development.

How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.

Lowry et al. use embryonic motor neuron selector transcription factors to partially rejuvenate the gene expression profile of mature neurons, making them more resistant to an ALS model without compromising their normal function.

Hardcastle and Marshall et al. show that striatal function is domain specific, required for task-related but not spontaneously expressed movements. This functional distinction is reflected in starkly different kinematic codes across the domains.

The mechanisms linking neuropsychiatric and metabolic disorders remain unclear. The authors show a pancreas–hippocampus feedback loop whereby metabolic and circadian factors drive behavioral fluctuations, with potential relevance for bipolar disorder.

By selectively isolating and sequencing the rare RNA transcripts containing C9orf72 repeat expansion from ALS–FTD neurons, the authors uncover an alternative splicing mechanism that explains the retention of this intron segment in a translated mRNA.

The principal layer architecture of the sensory cortex is altered with aging. The authors show that overall thinning of the primary somatosensory cortex is driven by deep layer degeneration but that layer IV is more pronounced in old age.

Machine-learning-augmented single-nucleus transcriptomic analysis compared molecular landscapes of immature neurons in the mammalian hippocampus across species, highlighting human-specific gene expression but convergent biological processes.

Activation of G_s signaling at mitochondria by mitoDREADD-G_s increases mitochondrial metabolism, leading to better memory in mouse models of dementia, directly linking brain mitochondrial deficits to cognitive symptoms of neurodegenerative diseases.

Parkinson’s disease (PD) involves toxic protein buildup and energy failure in neurons. Continuously breathing low-oxygen air protected mice from PD-like neuronal loss and reversed symptoms, even after they began, suggesting that hypoxia may protect neurons.

Ravenelle et al. show that systematically increasing serotonin has sex-specific effects on fear learning in mice. In females only, increasing serotonin in the BNST enhances fear memory by promoting communication with the amygdala.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Here the authors provide a comprehensive transcriptomic dataset of human primary microglia for Alzheimer’s disease and healthy aging. They identify dysregulation of immune-related microglial functions as a hallmark of disease.

The topographical organization of cells in the hippocampus reflects its ability to regulate mood and cognition. Here the authors generate a spatially resolved gene expression map in the human hippocampus to enable cross-species and functional interpretation.