Molecular and cellular mechanisms of nervous system function, including synaptic transmission, ion channels, neurotransmitter receptors, signal transduction, and neuronal development
12 papersThis study used human genetic data and mouse models to identify SLC45A4, a gene encoding a polyamine transporter, as being associated with chronic pain intensity, particularly for heat and tonic pain. Mice lacking this gene had reduced sensitivity to these types of pain, alongside changes in polyamine levels. The study also found changes in GABA levels in the spinal cord of knockout mice.
Molecular dynamics simulations suggest that neurotransmitter release is accomplished by a highly cooperative machinery whose calcium-triggered unclamping and membrane-fusing functionalities are intrinsically inseparable. The model reproduces experimental dependencies, providing a unified account of calcium-triggered unclamping and SNARE-mediated membrane fusion, which occur as contemporaneous and coupled processes.
This study found that in a mouse model of Alzheimer's disease, early loss of noradrenergic axons in the olfactory bulb leads to decreased sense of smell. This axon loss is driven by microglia, the brain's immune cells, which recognize and eliminate the axons. Early LC axon degeneration and increased microglial activity were also observed in post-mortem human olfactory bulbs, as well as increased TSPO signals in prodromal AD patients suggesting similar mechanisms may be at play in humans.
This study in Drosophila demonstrates that changes in mitochondrial dynamics within specific sleep-inducing neurons contribute to sleep pressure. Manipulating these mitochondrial processes can increase or decrease sleep duration and alter the flies' response to sleep deprivation. This suggests a fundamental connection between energy metabolism and sleep regulation.
In mice, impaired meningeal lymphatic drainage leads to altered synaptic balance in the brain, specifically a reduction in inhibitory synaptic transmission, which results in memory deficits. This effect is mediated by microglia and excessive interleukin-6 (IL-6) signaling. Enhancing lymphatic function in older mice reversed these synaptic and behavioral changes.
This study in fruit flies found that sleep deprivation leads to changes in gene expression related to mitochondrial function and dynamics in specific sleep-inducing neurons. Manipulating mitochondrial dynamics in these neurons alters sleep duration and neuronal excitability, suggesting a link between mitochondrial function and sleep pressure. Further research is needed to confirm a causal link and extend these findings to mammals.
This study created a single-cell spatial transcriptomic atlas and a whole-brain connectivity map of the macaque claustrum. It revealed four distinct zones within the claustrum, each containing unique compositions of glutamatergic cell types that project to specific cortical and subcortical regions. Notably, some of these glutamatergic cell types, found only in macaques, show preferential connections related to memory and motor function.
Unconnected glioblastoma cells, particularly those with neuronal and neural-progenitor-like characteristics, are the main drivers of brain invasion. These cells receive synaptic input from neurons, which stimulates the formation of tumor microtubes and accelerates their Lévy-like movement pattern, enabling them to efficiently colonize new brain regions.
The Neuropixels 2.0 probe allows stable recordings from thousands of sites in freely moving mice and rats over timescales exceeding two months, thanks to its miniaturized design, improved site density, and a novel motion correction algorithm. The probe also features a double-bank recording strategy for increased coverage, albeit with a trade-off in signal-to-noise ratio, and a recoverable design for re-implantation.
This study presents a draft human pangenome reference based on 47 phased diploid assemblies from diverse individuals. These assemblies, along with generated pangenome graphs, reveal new alleles, improve variant discovery (especially SVs), and enhance read mapping accuracy in various genomic applications, reducing bias inherent in single-reference approaches like GRCh38.
This connectomic analysis of the Drosophila central complex (CX) revealed circuit motifs that support flexible navigation and context-dependent action selection. The CX integrates diverse sensory cues to generate a stable head direction representation, updates this representation with self-motion information, and uses phase shifts in FB circuitry to perform vector-based computations, potentially enabling path integration and other goal-directed actions, while also modulating circuits involved in sleep, circadian rhythms, and nutrient homeostasis.
This study analyzed the connectome of the *Drosophila* mushroom body (MB), revealing a higher-than-expected level of visual input and a new class of "atypical" MBONs that integrate information from both inside and outside the MB lobes. The research also uncovered intricate connectivity patterns between MBONs and DANs, providing insights into the neural mechanisms underlying associative learning.