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Organoid modeling of human forebrain development reveals an opposite imbalance in excitatory neuron number in macrocephalic and normocephalic autistic probands, stemming from divergent expression of transcription factors driving cell fate.
Dominance behavior can influence social hierarchy. Here the authors show that cortical astrocytes can enhance excitatory and reduce inhibitory transmission via release of glutamate and ATP, which modulate dominance behavior, affecting the establishment of social hierarchy, among adult male mice.
The authors establish a connection between functional subtypes and genetic subtypes of dopamine neurons in mice and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions.
Tao et al. show that depressive-like behaviors in a female mouse model of ovarian hormone withdrawal can be attributed to downregulation of neuronal activity in Esr1 (estrogen receptor-1)-expressing GABAergic neurons in the medial preoptic area.
The mechanisms underlying motor arrest are unclear. Here, the authors show that Chx10+ neurons in the mouse pedunculopontine nucleus control global motor arrest in a pattern of pause (movement on hold) and play (movement resuming from the exact position it paused) likely in response to salient and nonthreatening environmental cues.
Complex spikes (CSs) driven by inferior olivary neurons have crucial roles in motor control. Wang et al. identified an excitatory pathway from the cerebellar nuclei to the inferior olive that drives rapid feedback CSs and contributes to the fine control of ocular and body movements.
The authors derive a neural network theory of systems consolidation to assess why some memories consolidate more than others. They propose that brains regulate consolidation to optimize generalization, so only predictable memory components consolidate.
Chandelier cells organize neural coding and mediate learning by establishing inhibitory circuit motifs over individual pyramidal neurons and suppressing irrelevant activity via adaptive axo-axonic synaptic plasticity, subserving efficient computation.
Sebenius et al. present Morphometric INverse Divergence (MIND), a robust MRI-based metric of similarity between brain areas that reflects biological factors that define cortical network architecture, such as gene expression and axonal connectivity.
The factors that regulate astrogenesis during development are not completely understood. Here the authors propose a data-driven framework to leverage transcriptomic data to identify ligand–receptor pairs promoting astrogenesis and validate their effects in human cortical organoids and fetal progenitor cells.
The cellular and molecular mechanisms underlying major depressive disorder are unclear. Here, the authors report cell type- and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behavior in female non-human primates.
To understand how antipsychotics modulate neural activity in the striatum, Yun et al. used in vivo imaging and found a correlation between clinical efficacy and the modulation of D1R-expressing, rather than D2R-expressing, striatal neurons in mice.
Changing temperature in striatum warped neural activity in time and categorical time judgments in rats. Similar effects on movement were not observed. Striatal dynamics may thus support discrete decisions and not continuous motor control.
Using direct recordings from human MTL neurons during sleep, Staresina et al. reveal that neuronal firing and communication—thought to underlie synaptic plasticity and learning—are controlled by coupled slow oscillations, spindles and ripples.
Dridi et al. identified a mechanism for cognitive dysfunction after heart failure in which hyper-adrenergic signaling and transforming growth factor-beta activation induced Ca2+ leak by RyR2 channels in hippocampal neurons.
The Dominantly Inherited Alzheimer Network neuroimaging repository is a free resource consisting of PET and MRI scans from 533 individuals across 206 families who are deeply phenotyped with genetic, clinical, cognitive and biofluid sampling.
Myelin is widely believed to protect axons from damage in multiple sclerosis. The authors challenge this view and find that myelin insulation renders axons more vulnerable to degeneration in an autoimmune environment.
Global reduction of m6A leads to mRNA stabilization in ALS/FTD caused by C9ORF72 repeat expansion. m6A also regulates repeat RNA decay. Elevating m6A reduces RNA and dipeptide repeats, restores mRNA homeostasis and improves patient neuron survival.
Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.
The authors find a surprising diversity in hypothalamic neurons projecting to habenula, and using patch-sequencing (Patch-seq), identify an estrogen receptor-expressing neuron type that signals aversion and is linked to stress in female mice.