European Journal of Neuroscience最新文献

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and a major genetic cause of autism spectrum disorders (ASDs). It results from the loss of fragile X mental retardation protein (FMRP), an mRNA-binding protein critical for synaptic development and plasticity. Although sensory processing abnormalities are well recognized in FXS, the olfactory system remains relatively underexplored in both human and animal studies. Evidence from rodent and drosophila models reveals that FMRP loss profoundly alters olfactory circuitry and function. In Fmr1 knockout mice, aberrant mitral cell dendritic morphology and increased granule cell spine density disrupt excitation/inhibition (E/I) balance, leading to circuit hyperexcitability and impaired odor discrimination. Similarly, dfmr1-deficient flies show reduced GABAergic inhibition, broadened odor tuning, and altered odor-guided behaviors, reflecting conserved mechanisms of synaptic dysregulation. These findings parallel disruptions seen in other sensory systems, underscoring the olfactory bulb as a microcircuit model for studying FXS-related neural dysfunction. Human evidence remains limited, but studies in ASD suggest that structural alterations in the olfactory bulb and prefrontal cortex may contribute to sensory deficits in FXS. Integrating findings across species, this review highlights the olfactory system as a translational framework for linking molecular dysfunction to circuit-level and behavioral abnormalities. By focusing on this well-characterized sensory network, it emphasizes how early synaptic and structural disruptions in FXS give rise to E/I imbalance and sensory processing impairments, providing insights into broader neurodevelopmental mechanisms and potential therapeutic targets.

Neuropathic pain (NP), particularly postherpetic neuralgia (PHN), involves intricate mechanisms that extend far beyond neuronal dysfunction. In recent years, glial cell-mediated neuro-immune-inflammatory circuits mediated by glial cells (including spinal microglia, astrocytes, and dorsal root ganglion satellite glia) have been regarded as one of the key pathological mechanisms for the occurrence and maintenance of NP. Glial cells exacerbate pain pathogenesis by driving neuroinflammation, amplifying nociceptive signaling, and modulating ion channels and pain-related signaling molecules. A systematic review of glial molecular and network alterations, correlated with the typical clinical phenotype of PHN, may provide practical clues for precise stratified therapy, drug repositioning, and novel targeted interventions (such as glial modulators, neuronutrition support, and neuro-immune pathway modulation). This review aims to summarize the latest progress in glial cells and neuropathic pain, with a focus on discussing its implications and suggestions for the treatment strategies of PHN.

Treatments for Parkinson's disease (PD) include medications like levodopa, surgical interventions such as deep brain stimulation (DBS), and rehabilitative approaches like exercise. While levodopa and DBS effects on the subthalamic nucleus (STN) are well studied, how exercise modulates this circuitry is less clear. This study investigates the acute and long-term effects of a monthlong motorized cycling intervention on STN activity, using local field potential (LFP) recordings from 29 electrodes placed in 18 STNs across nine PD patients (8/1 M/F; age 66.4 ± 9.7 years, UPDRS 20.7 ± 2.56). While the acute changes were minimal, the long-term changes in LFP features were more pronounced in the dorsal STN compared with its ventral region. Repeated exercise sessions produced a progressive increase in total LFP power in the dorsal STN, driven by elevations in the aperiodic background; the ventral STN showed no significant change over the same interval. This aperiodic modulation parallels increases typically observed with levodopa or STN-DBS, suggesting engagement of overlapping—but not identical—neuromodulatory mechanisms. To probe intra-STN coupling, we quantified dorsal–ventral interactions using the imaginary part of coherency (iCOH) and the phase slope index (PSI). PSI values remained near zero (|PSI| < 0.05), indicating minimal directed coupling, whereas iCOH increased in the 24–29-Hz range. Given the absence of connection and nonzero iCOH, we posited a shared upstream driver acting on both subregions. Using a statistical SSTr framework mathematically able to confirm the presence of this upstream “hidden” source.

Despite age-related declines in the structure and function of auditory and language-related regions, many older adults retain a relatively preserved ability to understand speech in noisy environments. However, the neural mechanisms supporting this ability remain unclear. In this study, 30 older adults (59–71 years) with normal hearing listened to narratives spoken by a separate group of speakers at varying noise levels, with their neural activity recorded using functional near-infrared spectroscopy (fNIRS). Speaker-listener neural coupling analysis revealed that older listeners' neural activity across broad brain regions, including classical language regions and the prefrontal cortex, was coupled with the speaker's speech-production-related neural activity. Compared to younger listeners, older adults exhibited stronger prefrontal neural coupling, which was stably integrated with language-region coupling across noise levels. Crucially, as noise levels increased, prefrontal neural coupling became more strongly correlated with comprehension performance. These findings elucidate the neural mechanisms supporting natural speech-in-noise processing in the aging brain, highlighting the compensatory involvement of the prefrontal cortex in facilitating speech-in-noise comprehension in older adults and indicating it as a potential target for neuromodulatory and cognitive interventions to promote successful aging.

Anxiety is a future-oriented mood state that consists of a complex cognitive, affective, physiological and behavioural response system that prepares individuals for perceived or anticipated threats. Although the neural circuits underlying anxiety behaviours have been extensively studied, how inflammatory factors influence anxiety and the molecular links between them remains poorly understood. To gain novel insights into these mechanisms, we investigated the role of fam19a5a, a zebrafish ortholog of the human FAM19A5 gene, which encodes a secreted peptide, in anxiety-like responses. Gene expression analyses revealed widespread fam19a5a expression in anxiety-associated brain regions, including the septum, pallial amygdala and habenula. Using multiple behavioural assays and both loss-of-function and gain-of-function genetic models, we found that the loss of fam19a5a significantly reduced anxiety-like responses. Interestingly, neuronal overexpression of fam19a5a also reduced anxiety-like responses. Neuronal activity analysis showed altered activity in the septum, pallial amygdala and habenula in fam19a5a-knockout brain without changes in neurotransmitter levels. However, increased neuronal activity was observed in the preoptic area of neuronal fam19a5a-overexpressing zebrafish. Transcriptomic analyses revealed upregulation of anti-inflammatory chemokines and cytokines and downregulation of proinflammatory factors, in both fam19a5a-knockout and neuronal fam19a5a-overexpressing brains. All together, these findings suggest that fam19a5a regulates anxiety-like behaviours in zebrafish by modulating the anti-inflammatory chemokine/cytokine signalling pathways.