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Benzodiazepines, used to treat anxiety and sleep disorders, may cause cognitive impairment. Shi et al. demonstrate that this is caused by interaction with the mitochondrial protein TSPO, which drives microglia to excessively remove synapses.

Heterochromatin loss has been linked to aging and neurodegeneration. Here, the authors show that combined loss of HP1β and HP1γ in neurons results in de-repressesion of endogenous retroviruses, inflammation in glia including accumulation of complement C3, dendritic loss, and cognitive decline in mice.

Fruit flies need to appropriately respond to mixtures of attractive and repellent odors in their natural environment. Here, the authors propose that lateral inhibition between glomeruli activated by attractants or repulsive odors mediates the appropriate response.

How stable sensory and motor variables are represented in association brain areas such as retrosplenial cortex (RSC) during the performance of a cognitive task is not fully understood. Here authors show that mouse RSC can reliably store sensory information about the environmental context and trial outcome while exhibiting flexible coding of motor choice.

Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.

Fagarasan and colleagues show that excessive activation of T cells in mice deficient in the inhibitory receptor PD-1 causes a systemic decrease in tryptophan and tyrosine, which leads to deficiency in serotonin and dopamine in the brain and behavioral changes.

The authors report that neddylation is required for dendritic spine development and stability, and loss of neddylation in excitatory forebrain neurons leads to synaptic loss, impaired neurotransmission, and learning and memory deficits. The roles of neddylation in spine maturation and synaptic transmission could be attributed to neddylation of PSD-95.

Microglia rely on mitochondrial respiration to respond to demyelinating injury. However, mitochondrial respiration is not required to support microglial proliferation.

The molecular diversity of microglia has been described. Here the authors show that ARG1-expressing microglia are enriched in phagocytic inclusions and are involved in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also modulate cognition in a sex-dependent manner.

The authors show how predictive representations are useful for maximizing future reward, particularly in spatial domains. They develop a predictive-map model of hippocampal place cells and entorhinal grid cells that captures a wide variety of effects from human and rodent literature.

The gut virome is altered in a mouse model of chronic stress and is associated with changes in behavioural and immune response, which can be restored using faecal virome transfer.

Feeding and stress are deeply related to each other, yet neural circuits how they interact are not fully understood. Here, the authors show that the parabrachial-to-parasubthalamic nucleus pathway is involved in fear-induced feeding suppression.

Fingolimod is a sphingosine-1 phosphate (S1P) receptor modulator and an immune modulator in use as a treatment for the remitting-relapsing form of multiple sclerosis. Hait et al. show that the active form of fingolimod can inhibit neuronal class I histone deacetylases (HDACs), modulate gene expression in the brain and facilitate memory extinction. The authors also show spatial and associative memory deficits in mutant mice lacking the enzyme necessary for formation of the active form of fingolimod.

The authors report that the ultrastructure and plasticity of excitatory synapses connecting dentate gyrus and CA3 of the hippocampus are severely compromised in a transchromosomic mouse model of Down syndrome. These alterations are accompanied by unstable information coding by CA3 and CA1 place cells, which may contribute to aspects of impaired cognition in the disease.

Neural mechanisms underlying flexible navigation are not fully understood. Here authors reveal how neural circuits dynamically adapt navigational plans in response to new information. Hippocampal circuits balance possible goals based on how much behavioral change is needed while prefrontal circuits represent changing plans.

This study uses a transgenic mouse line expressing Cre-inducible astro-hM3Dq to study astrocytes’ role in neuroinflammation and cognition without the use of viral transduction, mitigating the potential side effects associated with standard techniques.

A pilot clinical trial evaluating metformin in patients with pediatric brain tumors shows that it is a safe approach resulting in improved cognitive function that is consistent with the recovery of adult hippocampal neurogenesis observed in mouse models.

Mutations that enhance the activity of protein kinase C alpha (PKCα) are associated with Alzheimer’s Disease. Here, the authors report that the enhanced activity of one variant, PKCα M489V, is sufficient to rewire the brain phosphoproteome, drive synaptic degeneration, and impair cognition in a mouse model.

The hippocampal dorsal CA2 enables the recognition of novel conspecifics. Kassraian et al. show that it is also required for discriminating safety- versus threat-associated conspecifics and that its disruption gives rise to generalized social avoidance.

Georgiou et al. found that the sex of the person performing experiments affects mouse behavior, including responses to stress and ketamine. This effect was mediated by corticotropin-releasing factor neurons in the entorhinal cortex that project to CA1.

In a randomized, double-blind, placebo-controlled trial comparing autologous mRNA-engineered BCMA-targeting CAR T cell therapy versus placebo in patients with generalized myasthenia gravis, a significantly higher percentage of patients exhibited a reduction in disease activity in the treatment arm than in the placebo arm.

Ageing affects several brain areas causing a decrease in cognitive abilities and memory. We find that increasing the endogenous potential of the hippocampus to generate new neurons throughout life rejuvenates learning and memory, indicating that neural reserves can be exploited during ageing to compensate for age- or disease-related cognitive impairments.

TGF-β signaling is required for microglial homeostasis, however the source of ligands in the adult brain is unknown. Here, the authors show that microglial homeostasis relies on microglia-derived TGF-β1 ligand via an autocrine mechanism, which is also important for astrocyte homeostasis.

A computational model predicts coordinated drift of neural receptive fields during noisy representation learning and recapitulates experimental observations in the posterior parietal cortex and hippocampal CA1.

Impairments in memory flexibility are associated with neuropsychiatric disorders such as PTSD and autism. Here, the authors report that the transcriptional repressor Wilm's Tumor 1 regulates synaptic plasticity leading to weakening of memory strength and enabling memory flexibility.

The molecular mechanisms underlying the dynamic nature of the female brain structure and function remain poorly understood. Here the authors characterise chromatin organization in the mouse female ventral hippocampus, finding it fluctuates with the oestrous cycle, and identify changes in chromatin organization associated with the transcription of genes important for neuronal function and behaviour.

Gomez et al. show that boosting angiotensin-converting enzyme expression in microglia promotes phagocytic clearance of Aβ and endolysosomal trafficking, driven by spleen tyrosine kinase signaling in the 5xFAD transgenic model of Alzheimer’s disease.

McNamee et al. develop a theory of entorhinal–hippocampal processing. Distributed entorhinal input drives hippocampal activity between distinct statistical and dynamical regimes of activity, thereby unifying several empirical observations.

Integration of chemogenetics with quantitative behavioral assays and whole brain activity mapping reveal how distinct cerebellar regions influence activity during flexible behavioral learning. Integration of chemogenetics with quantitative behavioral assays and whole brain activity mapping reveal how distinct cerebellar regions influence activity during flexible behavioral learning

Ilaria Bertocchi et al. use a mouse model of Grin2a dysfunction to show that activity-independent NMDA receptors are involved in audiogenic seizure generation. Their results suggest a role for NMDA receptors in maintaining an appropriate response to sensory stimuli and a potential mechanism for disease phenotypes in epilepsy patients with GRIN2A mutations.

The neuron-specific RNA binding protein NOVA1 has a single amino acid substitution unique to modern humans. Here, the authors characterize the evolutional specificity and the function of the substitution. Studies using humanized NOVA1 mice reveal its specific effects on splicing and vocalization.

This study demonstrates the opacity resolution and visual function improvement following intrastromal injection of quiescent corneal stromal keratocytes but not stromal fibroblasts. The keratocyte therapy recapitulates native cornea’s collagen fibril organization and proteoglycans.

Molecular mechanisms of attention-deficit hyperactivity disorder (ADHD) are not fully understood. Here the authors demonstrate a mutation in CDH2, encoding N-cadherin, that is associated with ADHD, and in a mouse model, delineate molecular electrophysiological characteristics associated with this mutation.

Early alcohol drinking confers greater risk for alcohol use disorder in women than men. Here authors show that ovarian-derived estrogen rapidly drives binge alcohol drinking via signaling with membrane-associated estrogen receptors in the extended amygdala.

Protein synthesis is required in distinct populations of inhibitory neurons in the mouse amygdala to store memories of danger and safety.

Altered fatty acid intake during pregnancy is associated with neurodevelopmental disorders. Here, the authors show that maternal omega-3 fatty acids deficiency results in altered microglia-mediated phagocytosis of synaptic elements leading to impaired cognitive functions in the offspring in mice.