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Uhlmann et al. show that the preclinical phase of Alzheimer’s disease may in fact be a relatively late manifestation of a much earlier pathogenic and targetable process of seed formation and propagation.
Alzheimer’s disease is often considered a disease of neurons. This study reveals that astrocytes are also impaired by the disease and that these cells contribute more to memory deterioration than previously thought.
Learning to suppress maladaptive behaviors is critical for good mental health. Kim et al. show that mice can be taught to suppress previously acquired motor responses by selective and properly timed stimulation of the cerebello-olivary pathway.
Using cryo-electron tomography to detect individual GABAA receptors in hippocampal synapses, we discovered a hierarchical and mesophasic organization of inhibitory postsynaptic density proteins that enables efficient synaptic transmission.
When co-cultured with activated microglia, iPSC-derived interneurons from individuals with schizophrenia and from healthy controls show defects in metabolic pathways, but only the interneurons from individuals with schizophrenia showed prolonged metabolic deficits.
The authors present an edge-centric model of brain connectivity. Edge networks are stable across datasets, and their structure can be modulated by sensory input. When clustered, edge networks yield pervasively overlapping functional modules.
Peripheral macrophages located along motor axons react differently to neurodegeneration compared to CNS microglia in ALS mice. Modifying peripheral macrophages suppresses proinflammatory microglial responses, shifting them toward neuronal support.
Donegan et al. show that hippocampal CA2 neurons contribute to social memory by encoding social novelty. Abnormal CA2 coding and social memory in a mouse model of the 22q11.2 microdeletion are rescued by blocking elevated CA2 TREK-1 K+ current.
Aoi et al. used a new dimensionality-reduction method to disentangle the contributions of different task variables to neural population activity, which revealed rotational dynamics in monkey PFC during context-dependent decision-making.
The authors show that a coordinated epigenetic priming event during memory encoding and consolidation facilitates promoter–enhancer interactions that are vital for the unique transcriptional output of reactivated engram neurons.
Kohro et al. identify a population of astrocytes located in the superficial dorsal horn of adult spinal cord (genetically defined by Hes5) that acts as a gate for locus coeruleus descending noradrenergic control of mechanosensory hypersensitivity.
This work by Tian and colleagues unveils the extraordinarily complex layout of the human subcortex by identifying 27 new functional regions that organize hierarchically across four scales and adapt to changing cognitive demands.
This study demonstrates that basal ganglia functional topography is maintained across and downstream of its output nuclei, and in closed loops. Focal stimulation of distinct striatal subregions induces distinct action, supporting a model of parallel behavioral control.
Kusick et al. capture snapshots of synaptic vesicle docking and fusion using a new time-resolved electron microscopy technique. They find that vesicles are replaced milliseconds after they fuse, which may contribute to short-term synaptic plasticity.
By analyzing hundreds of mice treated with a library of neuro- and psychoactive drugs, Wiltschko et al. show that Motion Sequencing can effectively discriminate and categorize drug effects and link molecular targets to behavioral syllables.
Kuan, Phelps, et al. used synchrotron X-ray imaging and deep learning to map dense neuronal wiring in fly and mouse tissue, enabling examination of individual cells and connectivity in circuits governing motor control and perceptual decision-making.
The ventral hippocampus is central in the processing of emotional information. Here, a combination of viral and sequencing approaches defines the organizational logic of the extended ventral CA1 circuit.
Chen et al. define previously unreported zebrafish astrocytes, provide new insights into vertebrate astrocyte development and lay the foundation for studying astrocyte function in the entire nervous system of an intact and behaving animal.
The authors demonstrate that strongly recurrent circuits inferred from neural activity, even with unlimited data from every neuron, are biased. Synapses are inferred between unconnected but correlated neurons. Inference based on non-equilibrium activity may help remedy this.