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Epilepsy is the most common childhood neurological disease, and nearly 20% of affected children develop drug-resistant childhood epilepsy (DRCE). Using single-cell analysis methods, Kumar et al. have identified pro-inflammatory interactions between microglia and T cells in brain tissue from individuals with DRCE. This work may help to identify therapeutic targets for DRCE.

We report light-gated channels in a fungus-like protist that are highly selective for K⁺ over Na⁺. These microbial rhodopsin channels, named kalium channelrhodopsins, enable robust inhibition of mouse cortical neurons with millisecond precision. In addition, kalium channelrhodopsins reveal a previously unknown potassium selectivity mechanism.

Single-cell analysis of immune cells from surgically resected human epileptic brain tissues showed heterogeneity and pro-inflammatory signaling in microglia and evidence for direct interaction of microglia with T cells.

Dong et al. show that proliferative neural progenitors in the developing neocortex preferentially undergo anaerobic glycolysis and generate a high level of lactate that coordinately regulates vasculature outgrowth and progenitor behavior.

The authors report a functional class of channelrhodopsins that are highly selective for K⁺ over Na⁺. These light-gated channels, named ‘kalium channelrhodopsins’, enable robust inhibition of mouse cortical neurons with millisecond precision.

By complementing spatial transcriptomics with high-resolution proteomics, Kaufmann et al. tracked a gradient of disease severity across the brains of patients with progressive multiple sclerosis, uncovering new therapeutic opportunities to slow disease.

Can studying individual differences in brain structure and function reveal individual differences in behavior? Analyses of MRI data from nearly 50,000 individuals may suggest that the possibility is fleeting. Although sample size is important for brain-based prediction, researchers can take other steps to build better biomarkers. These include testing model generalizability across people, datasets, and time points and maximizing model robustness by optimizing brain data acquisition, behavioral measures, and prediction approaches.

Green and O’Dea et al. identify that the embryonic zebrafish brain is colonized by a population of early-colonizing microglia that are dependent on lymphatic vessels, placing lymphatic cells at the epicenter of microglia development.

Cutando and colleagues show that changes in D2 dopamine receptor levels in cerebellar Purkinje cells alter sociability and preference for social novelty without affecting motor functions.

The solutions found by neural networks to solve a task are often inscrutable. We have little insight into why a particular structure emerges in a network. By reverse engineering neural networks from dynamical principles, Dubreuil, Valente et al. show how neural population structure enables computational flexibility.

Neural computations are envisioned as arising from either distinct function subpopulations or distributed collective dynamics. Dubreuil and Valente et al. examined recurrent neural networks trained on various cognitive tasks and found that a mixed-selective yet non-random subpopulation structure enabled flexible responding through gain-modulated latent dynamics.

Sensory systems compress representations while preserving information. Modeling of dopamine neuron responses and behavior during decision-making indicates that cognitive systems also compress representations as long as overall rewards are preserved.

Learning induces formation of dendritic spines, but their functional properties are unknown. The authors show that new spines bind new presynaptic inputs into preexisting spine clusters, generating locally coherent inputs representing learned behaviors.

Interrogation of neuronal autophagy in vivo in Alzheimerʼs disease mouse models identified deficient autolysosome acidification as the basis for extreme autophagic stress, yielding β-amyloid accumulation within intact neurons, which are the main source of senile plaques.