Research articles

Mice expressing humanized mutant tau exhibit synaptic loss and behavioral abnormalities in the absence of abnormal tau conformers, suggesting that hyperphosphorylated tau can be pathological, at least in tauopathies caused by tau isoform imbalance.

The trans-Tango genetic strategy, which mediates signaling across synapses, was adapted to identify neural connections in a vertebrate nervous system, with synaptic partners confirmed in the retina and spinal cord of larval zebrafish.

In recent years, valuable mRNA-based developmental atlases of the mouse brain have been made available. Here, the authors use single-cell mass cytometry to build a protein-based single-cell profiling of the developing embryonic and postnatal mouse brain.

Using intracranial recordings in pairs of humans cooperating in interactive games, this study shows fine-grained cooperation dynamics featured by state-dependent motives and the intrabrain and interbrain profiles of high-gamma activity in the amygdala and temporoparietal junction.

Duplication of the MECP2 gene (encoding methyl-CpG-binding protein 2) causes MECP2 duplication syndrome. Here the authors develop a Cas13Y system capable of targeting the MECP2 mRNA for degradation and reducing protein levels in the brain of humanized MECP2-transgenic mice and nonhuman primates.

Brain function requires the formation of diverse and specific synapses. The authors show that the molecular code specifying excitatory connectivity on Purkinje cells evolves in an input-specific manner with postnatal circuit maturation.

Ambroziak, Nencini, Pohle and colleagues identify a slowly emerging plasticity mechanism in a discrete set of hypothalamic preoptic neurons that is triggered by long-term heat exposure and that drives thermal acclimation to promote heat tolerance in mice.

Ventral striatal dopamine D3 and D1 receptors regulate motivation and reinforcement, respectively, through dissociable physiological actions.

Inhibiting CaMKII impairs short-term memory (STM) in mice during an avoidance task but does not affect long-term memory (LTM). This suggests that STM and LTM are processed differently, with CaMKII critical for STM but not LTM.

The retinal foveola in the primate eye is critical for seeing fine details, color, text and faces. Using ultrahigh-field functional magnetic resonance imaging, Qian et al discover that there is a highly specialized cortical brain region for processing foveolar information.

Maltese et al. show in mice that experiencing an adverse event affects future interaction with others experiencing the same stressor. These self-experience socioemotional reactions are orchestrated by the corticotropin-releasing factor system in the medial prefrontal cortex.

This study identifies parallel gut–brain pathways that fine-tune feeding. Distinct brainstem neurons and visceral afferents either sense esophageal stretch to regulate eating speed or detect gut nutrients to shape long-term food choices and satiety.

Axons have always been assumed to be cylindrical. Using in silico modeling and cryopreservation of tissues, Griswold et al. demonstrate that unmyelinated axons of the mammalian central nervous system exhibit pearls-on-a-string morphology through their entire length.

Individuals with autism spectrum disorder show neural patterns different from those of neurotypical individuals. Here the authors show that this variation reflects a computational trade-off between accurate encoding and fast adaptation tuned by the neural population response.

Lüthi and colleagues show that activity of the locus coeruleus (LC) is crucial for the cyclic alternation between non-rapid-eye-movement and rapid-eye-movement sleep. Stressful experiences during waking can disrupt LC activity in sleep, which disorganizes the sleep cycle and increases microarousals.

The authors determine the synaptic wiring diagram of a vertebrate circuit and reveal behaviorally associated modules. A model based on this connectome predicts neural coding and dynamics that are verified with calcium imaging data.

The Rett syndrome protein MeCP2 regulates gene transcription by binding to methylated DNA. Here the authors find that MeCP2 also regulates key neuronal genes by binding to nonmethylated DNA, providing new insights into the disorder.

Using cryo-electron tomography (cryo-ET) and proteomics, this study identifies the tethering of pathological tau filaments within defined brain extracellular vesicles in Alzheimer’s disease, shining light on the link between these vesicles and tau pathology.

Here Zhang et al. establish multiscale relationships that link postmortem cell-type distributions with the in vivo functional organization of the human cerebral cortex, as assessed through functional magnetic resonance imaging.

Jhang et al. identify a prefrontal–pontomedullary pathway that slows breathing and reduces anxiety in mice, where the pontine reticular nucleus converts excitatory prefrontal inputs into inhibitory signals to brainstem respiratory networks.