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Sun et al. analyzed 22,514 human brain vascular single-nucleus transcriptomes from 428 individuals and uncovered AD-related gene expression and cell–cell interaction linked to genetics, as well as vascular dysfunction in APOE-associated cognitive decline.
Zhao et al. identified β2-microglobulin (β2M) as an essential factor driving β-amyloid (Aβ) neurotoxicity and cognitive impairment in mouse models of Alzheimer’s disease (AD) and implicated targeting β2M–Aβ coaggregation as a strategy for AD therapeutics.
Hahamy et al. demonstrate that, at the transitions between narrative events, the human brain reactivates past information that is relevant for the understanding of the current narrative stage.
Reconstitution of TDP-43 filaments that exhibit sequence and morphological features similar to those found in the brain helps to uncover a new mechanism for the formation and propagation of pathology in amyotrophic lateral sclerosis and other neurodegenerative diseases.
This study tests a key hypothesis of cerebellar motor correction, showing that inputs to the cerebellum that drive errors during skilled movements are rapidly adjusted over trials to enhance motor accuracy.
Endocannabinoids are important modulators of synaptic transmission, although their mechanism of release is unknown. In this study, the authors found that endocannabinoid postsynaptic release is mediated by synucleins via a synuclein-dependent and SNARE-dependent mechanism.
Behaviors often consist of sequences of component actions. Cury and Axel identify distinct classes of sensory neurons that control the transitions between the components of egg laying in the fly that afford this behavior an adaptive flexibility.
Using the chronic brain recordings in the anterior cingulate cortex and orbitofrontal cortex in four participants with intractable chronic pain, this study identified objective neural biomarkers of subjective pain experience.
The authors associate a novel genomic risk score with a broad set of psychiatric symptoms in children. They trace the impact of associated genes on cerebellar developmental processes that originate in fetal life and endure through early adolescence.
Increased neuronal activity and reduced sleep quality emerge in the early stages of Alzheimer’s disease (AD). Calafate et al. show that the sleep–active hypothalamic MCH system is involved in neuronal homeostasis but fails in the early stages of AD.
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.
Tang et al. show that continuous language can be decoded from functional MRI recordings to recover the meaning of perceived and imagined speech stimuli and silent videos and that this language decoding requires subject cooperation.
In this study, Petrucco, Lavian et al. identify a circuit in the hindbrain of larval zebrafish that persistently encodes heading direction. Neurons of this network, of stereotypical morphology, inhibit each other to support ring attractor dynamics.
Mechanisms of cognitive resilience against Tau pathology are unknown. The authors show that inactivation of the microglial cGAS–interferon axis confers such resilience by preserving the neuronal expression of myocyte enhancer factor 2c.
Individual variation in fMRI-derived brain networks is reproduced in a model using only the smoothness (autocorrelation) of the fMRI time series. Smoothness has implication for aging and can be causally manipulated by psychedelic serotonergic drugs.
The authors develop a reward optimization framework to study sustained deliberation in nonhuman primates. As the computational complexity increased, animals deliberated longer and applied more complex reasoning strategies to optimize rewards.
Dopamine error signals are modeled as deviations from a single predictive stream. The authors show that in complex settings, these neurons access multiple predictive streams, reflecting beliefs in the timing and identities of expected rewards.
The authors combine functional imaging, electrophysiology and molecular identification to examine the inhibitory control of hippocampal memory traces and uncover a role for specific populations of interneurons in regulating memory reactivation events during learning.
How does the brain define a useful decision variable (DV) when many possibilities are available? The authors show that rather than committing to the DV used to solve the task, the mouse’s premotor cortex entertains several strategies in parallel.
To fight or not to fight? Wei et al. show that Esr1 cells in the mouse cMPOA encode the fighting capability of male opponents and use this information to suppress aggression toward superior opponents by inhibiting attack-mediating ventromedial hypothalamus cells.