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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.
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.
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.
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.
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.
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.
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.
Using in vivo imaging in zebrafish, we unveiled critical components (PSD-95, gephyrin and neuroligin-3) and dynamic properties of synapses between neurons and oligodendrocyte precursor cells (OPC). Furthermore, we showed that neuron–OPC synapses have a pivotal role in regulating OPC development and CNS myelination.
