Volume 28 Issue 6, June 2025

Eleanor Maguire was a visionary cognitive neuroscientist whose research transformed our understanding of how the brain supports memory, navigation, and imagination.

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.

Sleep has restorative properties, but the mechanisms remain largely unknown. A study in Drosophila melanogaster reveals that glia dynamically monitor metabolic changes in the brain that accumulate from effortful behavior, triggering the need for rest and sleep.

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 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.

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.

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.

The neuronal composition of the intestinal submucosal plexus is incompletely understood. Here Li et al. define their neuron classes, connectome and stepwise acquisition of identities.

White matter aging leads to degenerative and inflammatory changes. Here the authors show that microglial dysfunction exacerbates glial CXCL10 expression, harmful CD8⁺ T cell recruitment, myelinated axon damage and functional decline in aging mice.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

Neuron-specific DNA methylation and intragenic enhancers target the Rett syndrome protein methyl-CpG-binding protein 2 to regulate genes that delineate closely related neuron types, suggesting breakdown of fine-scale neuronal specification in developmental disorders.

Sznajder et al. identified a molecular link between autism and myotonic dystrophy, showing that a tandem repeat mutation in a single gene can disrupt splicing of multiple autism-related genes during brain development, leading to autism-like traits.

Employing pharmacology, genetics and all-optical approaches in zebrafish, Braaker et al. find that neuronal activity influences the growth of myelin sheaths along axons by signaling through metabotropic glutamate receptor 5 on oligodendrocytes.

Animals alternate between active periods and periods of rest or sleep. This study in fruit flies points to brain metabolism as a cause for this and shows that a network of glial cells interacting with neurons links brain function with the need for rest and sleep.

Navigation relies on detecting left versus right body asymmetries for gaze and course stability. A central three-layer optic flow-sensitive network with competitive lateral disinhibition extracts asymmetries from complex motion patterns.

GABA is the primary inhibitory neurotransmitter in the central nervous system. Using two-photon GABA imaging, Matsumoto et al. reveal over 40 GABA neuron types in the mouse retina, each uniquely filtering visual features.

Social status mediates individual differences in methamphetamine-seeking by modulating dopaminergic pathways. In subordinate rodents, the mesolimbic pathway is stronger, and the mesocortical pathway is weaker, whereas dominant rodents show the opposite pattern.

The authors show that behavior and dopamine responses track prospective, but not retrospective, contingency. These results are explained by temporal difference (TD) learning models, indicating that TD errors are a measure of contingency.

Using a spatial reasoning task in mice, the authors show that retrosplenial cortex encodes spatial hypotheses with well-behaved recurrent dynamics, which can combine these hypotheses with incoming information to resolve ambiguities.

How sensory signals from both sides of the body are integrated into a single percept is not well understood. Park et al. show that callosal signaling supports the integration of bilateral tactile stimuli in a state- and task-dependent manner.

Rogers et al. show that psilocybin enhances fear extinction, suppresses fear neurons and recruits extinction neurons in the retrosplenial cortex in mice, providing evidence that its effects are linked to individual-neuron reorganization.

The brain and body are necessarily connected. Here the authors show that brain blood flow and electrical activity are coupled with systemic physiological changes in the body.

Some neurons act like body-proximity sensors. The authors show that these neurons reflect the value of contacting or avoiding objects. Together, these neurons compose a flexible predictive model for interacting with the world near the body.

Autism is associated with inflexibility of brain dynamics. Watanabe and Yamasue show that TMS over the right superior parietal lobule while the brain is ‘stuck’ in a certain state reduces this rigidity and relieves various autistic traits.