Neuroscience bulletin最新文献

The temporal pole (TP), one of the most expanded cortical regions in humans relative to other primates, plays a crucial role in human language processing. It is also one of the most structurally and functionally asymmetric regions. However, whether the functional architecture of the TP is shared by humans and macaques is an open question. We used spectral clustering algorithms to define a cross-species fine-grained TP atlas with different anatomical connectivity patterns. We identified three similar subregions, two ventral and one dorsal, within the TP in both humans and macaques. The parcellation scheme for the TP was validated using functional gradient mapping, anatomical connectivity and resting-state functional connectivity pattern analysis, and functional characterization. Furthermore, in conjunction with the Allen Human Brain Atlas, we revealed the molecular basis for the functional connectivity patterns of each human TP subregion. In addition, we compared the hemispheric asymmetry in mean gray matter volume, anatomical connectivity fingerprints, and whole brain functional connectivity patterns to reveal the evolutionary differences in the TP and found different asymmetric patterns between humans and macaques. In conclusion, our findings reveal that the asymmetry in structure and connectivity may underpin the hemispheric functional specialization of the brain and provide a novel insight into understanding the evolutionary origin of the TP.

Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis, yet the underlying mechanisms remain elusive. The current study, using a Lipopolysaccharide (LPS)-induced septic rat model, revealed the hyperphosphorylation of tau and cognitive impairments, accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats. Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10) as a central regulator of neuroinflammation. LPS triggered CXCL10 secretion in astrocytes, and astrocyte-conditioned medium from LPS-treated astrocytes induced tau hyperphosphorylation and synaptic deficits. Recombinant CXCL10 recapitulated these effects in vitro and in vivo. Blocking CXCL10-CXCR3 interaction reversed tau phosphorylation, synaptic impairment, and cognitive decline. Mechanistically, CXCL10-CXCR3 interaction activated CaMKII, driving tau hyperphosphorylation, while CaMKII inhibition restored synaptic protein levels. These findings establish CXCL10 as a key driver of tau pathology in SAE and suggest CXCL10-CXCR3 as a therapeutic target for sepsis-induced cognitive impairments.

Children with autism often exhibit abnormalities in body weight, but the underlying mechanism remains unclear. SH3 and multiple ankyrin repeat domains protein 3 (SHANK3), a scaffold protein of the postsynaptic density, has been reported to be associated with autism. This study aimed to investigate whether and how SHANK3 influences body weight in the hypothalamic neuronal regulation of energy homeostasis. Adeno-associated viruses 9 (AAV9) carrying CMV-Cre and Agrp-Cre were stereotactically injected to restore SHANK3 expression in the arcuate nucleus (ARC) and agouti-related peptide (AgRP) neurons, respectively. Agrp-Cre mice were injected with AAV9-p38α^flox/flox to overexpress p38α. Activated p38α was generated by mutating both D176A and F327S in p38α. Inactivated p38α was constructed by mutating both T180A and Y182F in p38α. Metabolic analysis, immunoblotting, histological analysis, the glucose tolerance test, the insulin tolerance test, and body fat mass analysis were applied to investigate the underlying mechanisms by which SHANK3 regulates body weight. We reveal that SHANK3 regulates body weight via the p38α signaling pathway in the AgRP neurons of the hypothalamus. Shank3 knockout (Shank3^-/-) mice exhibit resistance to diet-induced obesity. Shank3 re-expression in the ARC or AgRP neurons increases body weight in Shank3 knock-in mice with an inverted allele (SKO). Overexpression or activation of p38α in AgRP neurons elicits resistance to diet-induced obesity. Inactivated p38α in AgRP neurons abolished the resistance to diet-induced obesity due to SHANK3 deficiency. Our findings suggest that the SHANK3-p38α siganling pathway in AgRP neurons regulates body weight balance in autism, revealing a promising therapeutic target for obesity in children with autism.

This review highlights advances in inner ear organoids (IEOs) as a novel platform for drug screening and disease modeling, particularly for hearing loss. IEOs, derived from embryonic stem cells, induced pluripotent stem cells, or tissue-specific progenitors, provide a physiologically relevant alternative to traditional animal models. Significant progress has been made in utilizing various cell sources, extracellular matrix materials such as Matrigel and hydrogels, and methods for controlling microenvironments through biochemical and biophysical signals. Applications of IEOs in drug screening, disease modeling, and personalized medicine enable exploration of hearing loss mechanisms and therapeutic testing. However, challenges remain, including the incomplete maturation of cochlear cells and difficulty replicating in vivo environments. Future research should focus on optimizing IEO generation, incorporating microfluidic technologies, and advancing high-throughput screening to enhance drug discovery and clinical translation.

Exploring the mechanisms underlying willingness to buy (WTB) will help us identify neural indicators for predicting the performance of innovative products. Using functional magnetic resonance imaging, we asked participants to view products created by combining two components, including high applicability new combinations (HANCs), which provide a novel and practical application; and low applicability new combinations (LANCs), which provide no additional value. First, we found that WTB generally involves activation of the parahippocampal gyrus. For HANC, activation in the pars opercularis of the inferior frontal gyrus (IFG oper) is associated with WTB. Second, representational similarity analysis revealed that for HANC, the interrelation between the elements and combinations in the IFG oper predicts WTB. Third, multivoxel pattern analysis found that classification accuracy in the IFG oper predicts the difference in WTB between HANCs and LANCs. In conclusion, WTB requires default mode network-based associative processing. For HANC products, executive control network-based processes are necessary for value construction.

Ultrasound neuromodulation shows promise for treating neurological disorders, but the underlying mechanisms remain unclear. Here, we developed an integrated surface acoustic wave (SAW) ultrasound chip enabling simultaneous electrophysiological recording and Ca²⁺ imaging of cultured hippocampal neurons to investigate neuronal excitability and synaptic transmission during ultrasound stimulation. This study revealed, for the first time, three distinct neuronal response patterns induced by SAW ultrasound: an immediate response showing rapid activation, a delayed response exhibiting facilitation after several minutes, and a non-response maintaining baseline activity. Ultrasound stimulation increased action potential firing, enhanced excitatory postsynaptic currents, and elevated intracellular Ca²⁺ levels. These effects were dependent on extracellular Ca²⁺ influx and primarily dominated by L-type Ca²⁺ channels. Our findings suggest that individual neurons exhibit heterogeneous responses to SAW ultrasound stimulation based on their intracellular Ca²⁺ levels and L-type Ca²⁺ channel activity. This integrated approach provides new insights into the cellular mechanisms of ultrasound neuromodulation while highlighting the potential of SAW technology for precise, cell-type-specific neural control.

Cerebral ischemia restricts cerebral blood flow (CBF), leading to unstable hemodynamics. Past studies of ischemia mainly focused on cortical CBF reduction. However, its impact on hemodynamic changes, especially temporal varying characteristics, remains poorly understood. Here, we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion-reperfusion, and measured the temporal variability and changes in laterality using a novel state-space method. This method was also applied to stroke EEG datasets to validate its effectiveness. After arterial occlusion, the left marginal motor, sensory, auditory, and visual cortices exhibited severe temporal variability impairments. The laterality analysis indicated that affected left regions showed inferior unilateral mean, inter-hemispheric transition probability, time fraction, and laterality duration, while the right side had a higher laterality time fraction and duration. These impairments recovered partially following blood flow restoration. Besides, the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance. Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere. The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.