Volume 28 Issue 11, November 2025

The promise of genomics-focused neuroscience to improve health outcomes for Indigenous Peoples depends on ensuring more equitable data relationships though culturally appropriate data governance and the technical infrastructure to enable its implementation. Although ethical frameworks and legal policy mechanisms affirm Indigenous rights, there is a persistent gap in translating these commitments into practice. Here we discuss how embedding Indigenous data governance across research infrastructures and data ecosystems is needed to strengthen the field’s capacity to deliver beneficial outcomes for all.

In amyotrophic lateral sclerosis (ALS), nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 cause widespread dysregulation of mRNA splicing. Two recent studies have now revealed that loss of TDP-43 also affects mRNA 3′ end cleavage and polyadenylation, further influencing mRNA metabolism and protein expression.

Functional connectivity analyses using ultra-high precision 7 Tesla functional MRI identified a unified system for allostasis and interoception that included more than 96% of the anatomical connections documented in non-human animal tract-tracing studies. This whole-brain system included densely interconnected regions thought to form the backbone of neural communication across the brain.

Zeng et al. show that TDP-43, known for repressing cryptic exon usage in frontotemporal dementia/amyotrophic lateral sclerosis, also controls alternative polyadenylation, impacting expression of disease-linked genes (SFPQ, NEFL and TMEM106B).

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Ionescu, Ankol et al. show that, in ALS mouse and iPSC models, TDP-43 aggregation at NMJs stems from aberrant axonal translation, normally repressed by muscle EV-derived miR126. Loss of miR126 in ALS increases TDP-43 buildup, impairs local synthesis and triggers degeneration.

This study shows that C9orf72 mutations impair immune activation in ALS, affecting how brain cells communicate, and highlights key differences in the cellular and molecular pathways underlying sporadic and genetic forms of the disease.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Buron et al. show that oxytocin enhances heart rate variability linked to breathing during recovery from stress. This calming and cardio-protective effect is produced through a hypothalamus–brainstem pathway for parasympathetic control of the heart.

Figge-Schlensok et al. show that leptin-sensitive neurons in the lateral hypothalamus encode anxiogenic stimuli and facilitate adaptive strategies to enable an animal to overcome anxiety in threatening situations.

Xu et al. reveal that a bottom-up neural circuit from the medial septum to the subfornical organ prevents overhydration in mice by integrating oral and gastrointestinal signals before osmolality changes, demonstrating precise drinking control mechanisms.

Hammo et al. show that a single dose of psilocybin rapidly and sustainably relieves both chronic pain and anxiodepressive-like behaviors in mice by restoring prefrontal activity through partial agonism at 5-HT_2A and 5-HT_1A receptors.

Lai et al. show a function of astrocytic Ca²⁺ in preventing synaptic depotentiation by reducing repetitive dendritic activity in the motor cortex during motor training, thereby contributing to learning-dependent neuronal circuit modification.

The face reveals more than just emotion. Cazettes, Reato and colleagues show that subtle facial movements reveal hidden cognitive states, reflecting the brain’s ongoing computations and offering a noninvasive window into unexpressed thoughts and decisions.

Neurons that respond emergently to illusory contours drive pattern completion in V1. Pattern completion in lower cortical areas may therefore mediate perceptual inference by selectively reinforcing activity patterns that match prior expectations.

Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI studies of psychedelics.

Working memory improves during adolescent brain development. Zhu et al. tracked monkeys through adolescence, revealing that maturation of white matter tracts and refinement of neural firing patterns sharpen working memory precision.

Temporal integration throughout the human auditory cortex is predominantly locked to absolute time and does not vary with the duration of speech structures such as phonemes or words.

Sheehan et al. have characterized the circadian translatomes of astrocytes and microglia in the mouse cortex in the context of amyloid pathology or aging, revealing cell- and disease-specific reprogramming of neurodegeneration-related pathways.

The brain is constantly monitoring the systems in the body. Here the authors use 7 Tesla functional magnetic resonance imaging to map a large-scale brain system for body regulation in humans, including brainstem nuclei, and confirm many monosynaptic connections traced in nonhuman animals.

Brain clearance mechanisms are challenging to visualize in humans. Using magnetic resonance imaging, the authors noninvasively mapped cerebrospinal fluid motion across the brain, showing region-specific drivers in healthy participants and altered dynamics in cerebral amyloid angiopathy.