Neuroscience bulletin最新文献

The primary somatosensory barrel cortex (S1BF) plays a key role in sensory perception and sensorimotor feedback during self-grooming and exploratory whisking. However, whether neurons in the S1BF exhibit distinct activation patterns during the processing of sensory and motor information in these contexts remains unclear at the single-cell level. In this study, using miniature two-photon imaging (mini-2P) to monitor calcium transients, we identified four distinct neuron types based on their behavior-specific activation patterns: initiation-specific neurons (active at the onset of self-grooming (GIA cells) and whisking (WIA cells)) and sustained-response neurons (active throughout self-grooming (GDA cells) and whisking (WDA cells)). GDA neurons were engaged during both self-grooming and whisking, while WIA and WDA cells showed whisking-specific responses, becoming inactive during self-grooming. Our study reveals distinct neuronal responses in the S1BF during self-grooming and whisking, highlighting the differential processing of sensory and motor information by different neuronal populations.

This study reveals that maternal stress during pregnancy (MSDP) increases anxiety susceptibility in male offspring through Corticotropin-Releasing Factor Receptor 1 (CRFR1)-mediated time-specific hyperactivation of medial habenula (MHb) cholinergic projections to the interpeduncular nucleus (IPN). Male MSDP offspring exhibited heightened anxiety-like behaviors following 30 minutes of acute restraint stress (ARS). In vivo calcium imaging showed excessive activation of MHb ChAT-IPN projections specifically during the late phase (25-30 min) of ARS in MSDP offspring. Chemogenetic and optogenetic manipulations confirmed that this time-specific circuit hyperactivation drives anxiety susceptibility. Mechanistically, MSDP upregulated CRF/CRFR1 in the MHb. Pharmacological experiments demonstrated that CRFR1 activation directly enhances circuit activity. CRFR1 overexpression recapitulated MSDP phenotypes by increasing circuit activity and anxiety, while CRFR1 antagonism reversed both circuit hyperactivation and anxiety behaviors. Chemogenetic circuit inhibition blocked CRFR1 overexpression-induced anxiety, confirming that CRFR1 drives anxiety through this pathway.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by poly-glutamine expansion in the mutant huntingtin (mHTT) protein. While the pathogenesis involves both cell-autonomous and non-cell-autonomous mechanisms, the role of specific intercellular crosstalk in HD remains unclear. The PLP-150Q mouse model, which expresses mHTT selectively in oligodendrocytes, serves as an excellent platform for studying the progression of HD in these cells. RNA sequencing of PLP-150Q mouse brains revealed significant alterations in immune-inflammatory pathways and glial dysfunction, particularly in the corpus callosum and striatum. Notably, we observed an age-dependent upregulation of key inflammatory factors specifically within the corpus callosum. Western blot and immunohistochemical analyses further demonstrated reactive gliosis, characterized by elevated Iba1⁺ and CD68⁺ microglia, as well as GFAP⁺ and S100β⁺ astrocytes, alongside decreased myelin protein levels. Our findings suggest that mHTT in oligodendrocytes triggers age-dependent inflammation, contributing to HD progression and revealing new mechanisms in its pathogenesis.

Synapses, the core components of neuronal circuits, rely on precise ultrastructural and molecular organization to facilitate quantal transmission and plasticity, which underpin brain information processing and storage. Cryo-electron tomography (cryo-ET) has emerged as a powerful tool for elucidating the nanoscale architecture of synapses, yet prior studies have largely focused on synaptic vesicles and postsynaptic receptors, leaving other critical components underexplored. Here, we employed cryo-ET to quantitatively analyze subcellular features across over 300 intact hippocampal synapses, revealing: (1) A significant proportion of excitatory synapses (32%) localized to dendritic shafts, while a relatively high proportion of inhibitory synapses targeted dendritic spines (35%), with synaptic clefts displaying four distinct geometries; (2) Diverse structures, including dense core vesicles, membraneless dense granules, and empty clathrin cages were enriched within presynaptic boutons; (3) Mitochondria prevalent in both pre- and postsynaptic regions, showing higher abundance of mitochondrial matrix granules postsynaptically. These findings provide a comprehensive view of the structural organization within hippocampal synapses and suggest fundamental principles governing their subcellular architecture.

Polymodal sensory neurons integrate diverse stimuli for environmental perception, but their modality discrimination mechanisms remain unclear. We focused on Caenorhabditis elegans inner labial type 1 (IL1) neurons, key polymodal neurons mediating mechanical and cold responses, and identified a hierarchical channel system supporting their multimodal function. Specifically, DEG-1 sodium channels are dedicated mechanotransduction receptors; GLR-3 glutamate receptors are the main rapid cold sensors, driving cold-induced calcium signals and behaviors; TRPA-1 bidirectionally modulates mechanical adaptation via calcium signaling and promotes cold-related longevity. This framework reveals a polymodal design logic: dedicated channels (DEG-1/GLR-3) process discrete modalities in parallel for specificity, while TRPA-1 regulates both. Our work provides a molecular blueprint for IL1's precise stimulus processing, offering insights into conserved multimodal integration mechanisms across lineages.

The development of a complex nervous system relies on precisely regulated heterogeneity and population stability among multiple types of neural stem cells (NSCs). In Drosophila melanogaster, the larval NSCs consist of type I neuroblasts (I NBs) and type II neuroblasts (II NBs). While the division pattern of II NB lineages is similar to the cortical expansion of primates, the detailed mechanism governing their maintenance is still not completely understood. Here, we demonstrate that the N-myristoyl transferase (NMT) in Drosophila serves as a critical regulator to maintain II NBs identity through N-myristoylation. Mechanistically, NMT myristoylates the proteasome subunit P26s4 that negatively regulates Hairless, an antagonist of Notch, consequently sustaining normal Notch activity. In human brain organoids, the function of NMT is conserved in the maintenance and proliferation of NSCs. Overall, this research not only reveals significant roles of NMT and N-myristoylation in II NB maintenance but also highlights a novel mechanism of how post-translational modification (PTM) regulates the homeostasis among heterogeneous NSCs during neurogenesis.

Interleukin-33 (IL-33) regulates immune responses in central nervous system diseases. This study investigates the effect of IL-33 on astrocyte phenotypic transformation in Parkinson's disease (PD). The associations of IL-33, soluble growth-stimulating expression gene 2 (sST2), with PD severity and clinical symptoms were examined. IL-33 supplementation and knockdown were applied in vivo and in vitro to assess IL-33's impact on neuron loss, astrocyte polarization, and inflammation. Transcriptome sequencing was conducted to identify hub genes and pathways regulated by IL-33 in astrocytes, with validated in primary astrocytes. Plasma sST2 levels were elevated in PD patients and correlated with PD severity, while IL-33 decreased with disease progression. In PD models, IL-33 supplementation improved PD-like symptoms and A2 astrocyte polarization. Conversely, IL-33 knockdown worsened PD-like symptoms and neurotoxic polarization. RNA-seq identified the PENK-ERK/MAPK pathway as the key regulator of IL-33-mediated astrocyte transformation. In conclusion, IL-33 plays a crucial role in regulating astrocytes in PD.