Reviews & Analysis

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.

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 neuroimaging of individuals before and after they underwent an arm amputation shows that the map of the missing limb in somatosensory cortex remains stable after amputation, with no evidence of reorganization of either the hand or the face, challenging long-standing theories of brain remapping after limb loss.

When navigating through the world, we can predict our next location on the basis of an internal sense of our location and velocity, but we can also orient to external visual sensory cues to update and stabilize this sense of location and velocity. A new experiment that mismatches the speed of visual cues and physical movement in rats shows that hippocampal network dynamics rapidly alternate between these functions within cycles of the 8-Hz theta oscillation. In one portion of the theta cycle, the internal sense of location drives the phase of firing independent of visual cues or self-motion cues, whereas in the other portion, the phases depend on a match of visual and self-motion inputs, manifesting as a reduction in place cell activity when there is a mismatch.

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.

Recent advances in neuroscience have revealed how neural population activity underlying behavior can be well described by topological objects called neural manifolds. Understanding how nature, nurture and other factors shape neural manifolds could illuminate new avenues for defining mechanisms and interventions.

Binge drinking is widespread, but its underlying cellular mechanisms remain unclear. A recent study identifies a sparse ensemble of GABAergic neurons in the medial orbitofrontal cortex that is activated during binge drinking. These neurons send inhibitory projections to subcortical regions to limit alcohol intake, suggesting new strategies to reduce binge drinking and protect against alcohol use disorder.

To perceive events as simultaneous despite differences in how sensory signals are generated and transmitted, the brain must preserve temporal coherence. We found that retinal ganglion cells adjust the speed with which they transmit neural signals, revealing a mechanism in the human retina to keep visual perception precisely timed.

Direct and simultaneous recordings across the human brain during a memory encoding task involving emotionally valenced words revealed tightly clustered neuronal sites within the insular cortex with distinct roles — some tracked valence, whereas others predicted memory. Only memory-related insular sites, when electrically stimulated, sparked strong hippocampal responses, uncovering a specialized insula–hippocampus axis for successful memory encoding.

Despite the loss of neurons during aging and the early stages of neurodegenerative disease, many cortical brain functions remain remarkably intact. Although this resilience is traditionally attributed to redundancy in neural networks, a new study uncovers a more active mechanism: dynamic homeostatic processes that preserve cortical representations in the face of neuronal loss. These processes recruit previously unengaged neurons and rearrange neuronal activity patterns to compensate for neuronal loss and maintain the integrity of representational maps in the brain.

Aging is a primary risk factor for neurodegenerative diseases. This study shows that key RNA pathways are disrupted in old neurons, including splicing and the stress response. Because of these changes, the aging brain has reduced resilience to new stress, which might predispose old neurons to disease.

Certain neurons have visual and auditory receptive fields anchored to body parts. We show that these neurons reflect the value of interacting with objects near the body, not just their spatial locations. A collection of these neurons furnishes animals with an egocentric map: a predictive model of the near-body environment.

This review explores how stroke induces changes in gene expression, cell behavior and brain networks, offering insights into recovery. It highlights strategies to enhance cellular reprogramming and brain network reorganization for improved outcomes.

In mouse models of epilepsy and human brain samples, hyperactive inhibitory signaling from neurons and complement signaling from astrocytes coordinate to drive microglia-mediated selective elimination of inhibitory synapses. This positive feedback mechanism disrupts the excitatory–inhibitory neurotransmission balance, which exacerbates neuronal hyperexcitability and contributes to the pathophysiology of epilepsy.

How does the brain learn to predict rewards? In this issue of Nature Neuroscience, Qian, Burrell et al. show that understanding how dopamine guides learning requires knowledge of how animals interpret tasks — what they believe is happening and when. By carefully manipulating cue–reward contingencies, the authors show that dopamine responses track belief-state reward prediction errors. These findings reaffirm — against recent challenges — that mesolimbic dopamine neurons signal prediction errors in line with the temporal difference learning rule, a core algorithm that bridges neuroscience and artificial intelligence.

Aging induces pathological changes in central nervous system (CNS) myelin, which in turn induce microglia dysregulation. What is the consequence of this microglial response on white matter pathology in aging? Groh et al. show that a maladaptive white matter-associated microglia state that emerges in aging recruits peripheral T cells to the CNS, which leads to degeneration of myelinated axons and loss of function.

Sankowski and Prinz propose a classification framework for microglia states that considers the contextual plasticity of microglia. Their multimodal classification aligns a robust terminology with biological function and cellular context.

Widespread, slow fluctuations in brain blood flow detected via functional MRI and neural activity are integrated with systemic physiological dynamics across the body. We showed this brain–body integration associates with the arousal response orchestrated by the autonomic nervous system.