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In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.
Many animals rely on internal representations of continuous variables such as head direction to guide behavior. Noorman et al. show how such representations can be accurately maintained in small neural networks, countering decades of theoretical intuition.
Matoba, Le, Valone et al. characterized context-dependent genetic effects on gene regulatory activity during Wnt stimulation, finding that genetic variant function during neurodevelopment patterning can lead to differences in adult brain traits.
Chen et al. show that subtypes of immune cells in prenatal human brain promote angiogenesis in the germinal matrix. Conversely, in preterm infants, proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage.
The authors review current knowledge of the molecular identity and functions of the dura, arachnoid and pial layers of meninges and controversial aspects of meningeal biology that deserve further study to resolve ongoing debates in the field.
Jung et al. show that shelter experience boosts dopamine release in the nucleus accumbens, generating a goal-location memory. Reactivating a neuronal ensemble developed from shelter experience enables memory-guided navigation to the goal during escape.
Siddiqi et al. identified lesion locations that reduced probability of PTSD. These were connected to a brain circuit in which increased connectivity was associated with PTSD, thus revealing a PTSD target circuit for therapeutic brain stimulation.
The authors perform the first single-cell profiling of m6A in the mouse brain. They uncover relative hypomethylation of microglial mRNA compared to other cell types, and they identify hundreds of RNAs that undergo differential methylation with age.
Neuronal recordings show that primate superior colliculus encodes learned abstract visual categories. The authors demonstrate that it plays a causal role in categorization behavior, independent of its role in spatial orienting.
Gallego-Rudolf et al. report accelerated brain activity with initial amyloid-β deposition in asymptomatic individuals. In those where tau also starts accumulating, brain activity decelerates, correlating with subsequent cognitive decline.
ApoE4 is a risk factor for Alzheimer’s disease and vascular dementia. We report that in ApoE4 mice perivascular macrophages are the sole source and effectors of the ApoE4 mediating the neurovascular dysfunction, enhanced white matter damage and cognitive impairment.
Early in Alzheimer’s disease (AD), brain blood flow is reduced by pericytes constricting capillaries. Korte et al. show that oral nimodipine can reverse this and decrease brain hypoxia. Blocking capillary constriction is a potential add-on therapy in AD.
This study shows that the brain can link action to value through neural population subspaces, balancing reliable binding of action to value and generalization to novel stimuli.
Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.
Neural changes in pregnancy are not well understood. Here Pritschet et al. present an open-access precision brain imaging resource, mapping neuroanatomical change in an individual from preconception through postpartum.
Tonic and burst-like locus coeruleus firing distinctly tune brain topology toward associative and sensory regions, recruiting both astrocytic and neuronal inhibitory activity.
We reveal that lipid turnover in the myelin sheath generates a fatty acid pool in oligodendrocytes that can contribute to the energy balance of white matter tracts. We also demonstrate that when glucose levels are limiting, fatty acid metabolism can support glial cell survival and the basic functional integrity of myelinated axons.
The mechanisms underlying the ability to remyelinate in aging and disease are unclear. Here, the authors show that DOR-mediated activation of α-ketoglutarate in mature oligodendrocytes can promote myelin production in mice during demyelination and aging.
