Research Briefing

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  • Independent of its appetite- and body weight-modulating effects, the hormone asprosin activates its receptor PTPRD at cerebellar Purkinje neurons to enhance thirst and maintain fluid homeostasis. Surprisingly, this has no effect whatsoever on Purkinje neuron-mediated motor coordination and learning.

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  • Neurons in the hippocampus of Egyptian fruit bats modulate their activity during a spatial reward task depending on the identity of the human experimenter at the goal location. A separate subpopulation of neurons carries significant spatial information about the positions and identities of humans traversing the same environment while bats are stationary.

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  • We present a developmental atlas that offers insight into sequential epigenetic changes underlying early human brain development modeled in organoids, which reconstructs the differentiation trajectories of all major CNS regions. It shows that epigenetic regulation via the installation of activating histone marks precedes activation of groups of neuronal genes.

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  • Specifically mutating the neurofibromatosis type 1 gene (NF1) in oligodendrocyte precursor cells (OPCs) impairs their adaptive response to neuronal activity and their differentiation into mature oligodendrocytes, as well as promoting focal regions of OPC hyperdensity. These defects delay oligodendroglial development and impede adaptive oligodendrogenesis, which are important for motor learning.

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  • By using genetic admixture in the multi-omic analysis of postmortem brains from Black Americans, we show that genetic ancestry influences gene expression in the brain. Notably, we find enrichment of ancestry-associated genes for immune response and vascular function, but not neuronal function. Our findings have potential implications for stroke, Parkinson’s disease and Alzheimer’s disease.

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  • Gene expression in the human cortex is shown to exhibit a generalizable three-component architecture that reflects neuronal, metabolic, and immune programmes of healthy brain development. The three components have distinct associations with autism spectrum disorder and schizophrenia, revealing connections between previously unrelated results from studies of case–control neuroimaging, differential gene expression, and genetic risk.

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  • In the first comprehensive mRNA isoform atlas of the developing and adult mouse brain, we discover that region and age influence the isoform repertoire of cell subtypes. We link peak cell type regulation to the critical development period and report attenuated levels in adulthood.

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  • Cold sensor identities in peripheral somatosensory neurons remain obscure. We show that GluK2, a kainate-type glutamate-sensing chemoreceptor that mediates synaptic transmission in the brain, mediates the sensing of cold but not cool temperatures in mouse dorsal root ganglia neurons in the periphery. Thus, we identify GluK2 as a cold-sensing thermoreceptor.

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  • Brain connections modulated by 534 deep-brain-stimulation electrodes revealed a gradient of circuits involved in dystonia, Parkinson’s disease, Tourette’s syndrome and obsessive-compulsive disorder. Together, these circuits begin to describe the human ‘dysfunctome’, a library of dysfunctional circuits that lead to various brain disorders.

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  • Long COVID has remained an on-going public health issue in the years following the global pandemic. Here, we report blood–brain barrier disruption in patients with acute SARS-CoV-2 infection and brain fog, and patients presenting with long COVID, brain fog and cognitive decline, compared to those with long COVID without any neurological symptoms.

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  • A widespread group of cerebellar projections form monosynaptic excitatory synapses with neurons throughout the substantia nigra pars compacta (SNc). These projections contain information associated with movement and reward and can rapidly increase SNc neuron activity, and thereby basal ganglia dopamine levels, which contribute to movement initiation, vigor and reward processing.

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  • This research elucidates that oligodendrocytes detect and respond to fast axonal spiking through K+ signaling, and that Kir4.1 channel activation has a pivotal role. This activity-driven interaction regulates axonal metabolic support by oligodendrocytes and influences lactate delivery and glucose metabolism in axons, which is essential for sustaining axonal health.

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  • We discovered expression of SYNGAP1, which encodes the ‘synaptic’ protein SYNGAP1, within human cortical progenitors. In an organoid model of SYNGAP1 haploinsufficiency, cortical neurogenesis and neuronal network activity were disrupted. This finding reveals an unknown function for SYNGAP1 at early stages of development, providing a new framework for understanding the pathophysiology of autism spectrum disorder.

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  • Sleep is typically considered as a state of behavioral disconnection from the outside world. Recordings of brain activity and facial muscle tone during sleep reveal that humans can respond to external stimuli across most sleep stages. These windows of behavioral responsiveness reveal transient episodes of high-cognitive states with electrophysiological signatures suggestive of a conscious state.

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  • We used single-nucleus sequencing to generate an atlas of gene expression and chromatin accessibility in the amygdala of outbred rats with divergent cocaine addiction-like behaviors. The results implicated dysregulation of metabolic pathways and GABAergic transmission as molecular bases of susceptibility or resistance to addiction.

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  • We developed a 3D human neuroimmune axis model to study the interplay of brain innate immune cells and peripheral adaptive immune cells in Alzheimer’s disease. Alzheimer’s disease pathology induced a marked increase in CD8+ T cell infiltration, exacerbating neurodegeneration. The CXCL10–CXCR3 pathway has a key role in mediating this process.

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  • Communication between diverse cell types is crucial to the development of the nervous system. However, the secreted signals that help to switch the cell fates of progenitor cells from neurogenesis to astrogenesis are not fully understood. Experiments in human tissues show that five ligands work together to push astrocyte generation and maturation.

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