Neuroscience bulletin最新文献

Vestibular efferent neurons in the brainstem provide direct cholinergic innervation to peripheral vestibular organs, thereby modulating their sensory responsiveness. In this study, a genetically targeted mouse model with choline acetyltransferase-driven fluorescent labeling enabled the precise localization of these neurons to the dorsolateral region of the genu of the facial nerve. Whole-cell patch-clamp recordings in acute brainstem slices revealed that virtually all neurons exhibited spontaneous action potential firing, with marked heterogeneity in discharge patterns and after-hyperpolarization kinetics. Prominent A-type potassium currents were identified and found to be differentially regulated by acetylcholine and calcitonin gene-related peptide. Acute unilateral vestibular deprivation induced a bilateral enhancement of spontaneous firing, indicating sensitivity to altered sensory input. These findings define the intrinsic electrophysiological properties and neuromodulatory mechanisms of vestibular efferent neurons, providing mechanistic insight into their roles in both physiological regulation and adaptive plasticity within the vestibular system.

A better understanding of neocortical architecture provides a means for its functional elucidation. In this study, we focused on the analysis of the lipidome composition in two human neocortical regions using laser-capture microdissection combined with mass spectrometry and mass spectrometry imaging. Among the 312 lipids detected in tissue samples representing discrete neocortical layers (L1, L3, and L5), three-quarters showed significant differences in abundance among layers, forming distinct patterns. Lipid distribution among these patterns depended on both the lipids' biochemical class and their fatty acid residue length and unsaturation. The assignment of lipids to cell types using spatial transcriptomics data suggested biological underpinnings of these patterns. Collected mass spectrometry imaging data further allowed for the reconstruction of lipid spatial distribution patterns across neocortical layers. These results reveal a complex relationship between lipids' biochemical properties and neocortical histological features, laying a foundation for further studies on the lipidome architecture of the human brain.

Deficits in BDNF/TrkB receptor signaling lead to increased asparagine endopeptidase activity, which cleaves Tau at the N368 residue to promote Tau hyperphosphorylation and aggregation, thereby contributing to neuronal dysfunction in Alzheimer's disease (AD). However, whether Tau N368 inhibits the BDNF/TrkB signaling pathway remains poorly understood. Previous studies have shown that the internalization of the BDNF/TrkB complex, which leads to signaling endosomes, is necessary for coordinating neuronal survival and synaptic plasticity. Here, we demonstrate that Bridging Integrator 1 (BIN1) interacts with the Tau fragment N368 in P301S and Tau N368-Tg mouse brains, inhibiting BDNF/TrkB signaling by obstructing their early-endosome recycling. Overexpression of BIN1 in the hippocampus of Tau N368-Tg mice partially rescues BDNF/TrkB endosome transport and alleviates pathological and behavioral defects. Our findings suggest that dysfunction of the early-endosome pathway mediated by the Tau N368-BIN1 interaction impairs BDNF signaling, contributing to AD-associated pathological and behavioral dysfunction.

GluN3B is the most recently identified subunit of N-methyl-d-aspartate receptors (NMDARs), and gradually it has been found that it may be involved in regulating the development of central nervous system (CNS)-related diseases. Compared with the traditional NMDARs containing only GluN1 and GluN2 subunits, non-classical NMDARs with GluN3 have non-conventional biophysical, trafficking, and signaling properties. As a negative regulatory subunit that diminishes or inhibits classical NMDARs' functions, GluN3B plays important roles in synaptic plasticity and neuronal survival, and may be associated with CNS disorders such as schizophrenia and substance use disorders. However, the number and depth of studies on how GluN3B is involved in the regulation of related diseases are very limited. This review summarizes the expression and physiological characterization of GluN3B-NMDARs and provides an overview of their emerging roles in psychiatric and neuropsychiatric disorders, aiming to provide a basis for understanding disease mechanisms and developing novel therapeutic targets.

Perioperative neurocognitive disorders (PNDs) represent a significant challenge in the perioperative setting, while the pathophysiology of PNDs remains unclear. Utilizing a murine model of abdominal surgery, we found that abnormal glutamatergic neurotransmission in the medial prefrontal cortex (mPFC) and hippocampus contributes to postoperative cognitive impairments. Increases in the frequency of miniature excitatory postsynaptic currents in both the mPFC and CA1 neurons indicate enhanced presynaptic glutamate release while having little effect on inhibitory neurotransmission. Surgery also enhances glutamate release from presynaptic terminals in the Schaffer collateral pathway. In addition, abdominal surgery increased the activation of microglia and astrocytes, elevated central inflammatory markers, and reduced excitatory amino-acid transporter-2 expression. Dexmedetomidine significantly mitigates the postoperative cognitive deficits by reducing inflammation and preserving neuronal structural complexity and dendritic spine stability, likely through inhibiting glutamate release and enhancing its reuptake. These findings advance our understanding of the etiology of PNDs and provide hints for potential intervention.

Brain disorders have imposed an escalating socioeconomic burden in recent years, yet critical gaps persist in understanding their pathogenesis and developing effective therapies. Nonhuman primate (NHP) models provide invaluable insights into human brain disorders due to their unique neuroanatomical and neurophysiological similarities with humans. Here, we review the current landscape of genetically modified NHP-based research in brain disorders, emphasizing the pivotal role of gene editing in disease modeling and the distinct advantages of transgenic NHP models in deciphering disease mechanisms. While key mechanistic questions and technical hurdles remain, NHP models hold immense promise in overcoming challenges and accelerating the development of therapeutics for brain disorders.

Cortical layer 2/3 plays a pivotal role in regulating perception and consciousness. However, the effects of anesthetic agents on the dynamic activity patterns in this layer remain poorly understood. This study examined how neuronal activity in cortical layer 2/3 dynamically changes under anesthesia. Using high-resolution wide-field microscopy, we performed whole-brain synchronous imaging of layer 2/3 neuronal activity in mice. Using these recordings, we performed an unbiased segmentation of the awake, anesthesia, and recovery stages and classified neurons into three categories according to their activity features. Our findings revealed the characteristics of cortical dynamics under anesthesia, including a rebound effect during recovery and nonlinear changes in neuronal activity. We also confirmed the consistent and uniform characteristics of superficial cortical layer activity under anesthesia. These results increase the understanding of cortical dynamics and provide a theoretical basis for improving clinical monitoring techniques and protocols.