Frontiers in Cellular Neuroscience最新文献

[This corrects the article DOI: 10.3389/fncel.2025.1681891.].

Neural stem cells (NSCs) hold significant potential in neural regenerative medicine, yet research faces multiple challenges such as cellular heterogeneity, unclear microenvironment interactions, and low clinical translation efficiency. In recent years, the rapid development of artificial intelligence (AI) technologies has provided new ideas and tools to address these issues. This paper reviews the current applications of AI in fundamental NSCs research, including intelligent identification, deep learning-driven subtype analysis, spatial microenvironment deconstruction, and dynamic analysis of neural differentiation. Additionally, we discuss several key AI technologies not yet applied to NSCs research, such as generative adversarial networks, graph neural networks, and self-supervised learning, as well as their potential applications in cell classification, interaction network analysis, and morphological feature extraction. Although AI technologies show great promise in NSCs research, challenges remain regarding data quality, model robustness, and interpretability. Therefore, future research should focus on establishing high-quality standardized multimodal data platforms and integrating biological knowledge to enhance model interpretability, thereby deepening the understanding of NSCs biological characteristics and differentiation mechanisms and advancing personalized therapies.

The discovery of neuronal activity-dependent calcium transients in astrocytes has driven the conceptualization of these cells as computational units in the nervous system. Tripartite synapses, consisting of pre- and postsynaptic terminals along with an adjacent astrocyte, enable astrocytes to communicate with and shape the activity of local synapses. In the hippocampus, astrocytes encode and modulate information through a variety of mechanisms, including tuning the gating of single synapses in their domains, coordinating oscillatory activity across neuronal circuits through astrocytic networks, and providing a foundation for long-term memory formation through intracellular signaling and metabolic coupling. The bidirectional and complementary activities of astrocytes and neurons can be situated in a framework that positions astrocytes as integrators and modulators of neuronal activity, both locally and globally. In this review, we focus on hippocampal astrocytes and discuss recent progress toward understanding astrocytic function in concert with neurons to mediate circuit function and, ultimately, behavior.

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of highly persistent organofluorine compounds, and extensively used in industrial and consumer application. Their environmental ubiquity and bioaccumulation in humans have raised concerns about potential health impacts, particularly on neurodevelopment. This mini-review synthesizes epidemiological and experimental research published between 2020 and 2025 examining prenatal PFAS exposure and neurodevelopmental outcomes in children. Prospective birth cohort studies from Europe, North America, and Asia report subtle but statistically significant associations between higher maternal PFAS levels and a range of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), cognitive delays (e.g., reduced IQ, language impairments), and behavioral dysregulation. Mechanistic investigations reveal that PFAS can cross the placenta, alter maternal-fetal thyroid and sex-steroid hormone homeostasis, activate inflammatory pathways (e.g., AIM2 inflammasome), disrupt neurotransmitter systems (notably dopaminergic and GABAergic signaling), modulate fetal metabolomic profiles, and induce durable epigenetic modifications. Key methodological challenges include heterogeneity of PFAS mixtures, reliance on single-time-point exposure assessments, variable confounder control (e.g., socioeconomic status, maternal IQ, nutrition, breastfeeding), limited follow-up into later childhood or adolescence, and sparse data on emerging short-chain PFAS analogs. To strengthen causal inference and inform public health interventions, future research should employ longitudinal designs with repeated biomonitoring, standardized neuropsychological assessments, advanced mixture-modeling approaches, comprehensive confounder adjustment, inclusion of vulnerable populations, and focused evaluation of replacement PFAS. Coordinated efforts bridging epidemiology, mechanistic science, and regulatory policy are essential to mitigate PFAS exposure and safeguard neurodevelopmental health in future generations.

Introduction: Immunological changes are implicated in the pathophysiology of depression. We aimed to assess phenotype and frequency of immune cell subtypes, including an assessment of regulatory T cells and production of cytokines by T cell subsets following stimulation.

Methods: Using a flow cytometric analysis, peripheral blood samples obtained from medicated patients with depression (n = 20) were analysed and compared to age-and sex-matched healthy controls (n = 21), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D24).

Results: A reduction in the frequencies of CD19+ B cells and IL-17+ CD8 T cells was evident in depressed patients compared to healthy controls. For a subgroup of depressed patients assessed pre- versus post-ECT, there was no change in phenotype, frequency or function of immune cell subtypes within 72 hours of completing treatment. Further exploratory analyses found that baseline CD16-CD14+ classical monocyte frequency correlated with change in HAM-D24 score post-ECT, indicating that a higher frequency of classical monocytes at baseline is associated with greater symptom improvement after treatment. A reduced number of CCR7-CD45RO+ effector memory T cells was also found to be associated with an improvement in symptoms post-ECT.

Discussion: Overall, these results demonstrate that flow cytometry is useful for immune profiling to identify altered adaptive immune features in depression and potential biomarkers of ECT response. In particular, changes in classical monocytes and effector memory T cells were associated with treatment response in patients with unipolar depression.

Astrocytes are connected in a functional syncytium via gap junctions, which contribute to the maintenance of extracellular K⁺ homeostasis. The prevailing hypothesis is that K⁺ released during neuronal firing is taken up by astrocytes via K _ir channels and then distributed among neighboring astrocytes via gap junctions. Here, we tested the effect of blocking gap junctions and K _ir channels, both independently and simultaneously, on field excitability of cortical slices in response to a stimulation train. Independently blocking either gap junctions or K _ir channels increased the amplitude of the first fEPSC (field excitatory post-synaptic current) response, followed by suppression of both fiber volley (pre-synaptic action potentials) and fEPSCs during sustained stimulation. Surprisingly, simultaneous block of both gap junctions and K _ir channels enhanced the suppression of neuronal activity, resulting in a ∼75% decrease in fiber volley amplitude in the first response, followed by a fast and strong suppression of fEPSCs during sustained stimulation. Genetic depletion of astrocyte gap junctions showed a reduction but not complete loss of Cx43, indicating partial syncytial decoupling, and, accordingly, had a weaker but similar effect on neuronal excitability as blocking gap junctions. Pharmacological K _ir block in mice with reduced gap junction coupling suppressed sustained firing of the fiber volley but not fEPSCs. That this effect was milder than K _ir block alone suggests that adaptive mechanisms may be recruited upon genetically induced astrocyte decoupling. We conclude that K⁺ buffering via K _ir and gap junctions in astrocytes together play a critical role in maintaining neuronal excitability, particularly during sustained activity, but that other mechanisms can be recruited to perform this function in their absence.

[This corrects the article DOI: 10.3389/fncel.2025.1590493.].

Introduction: The external segment of the globus pallidus (GPe) is traditionally viewed as a relay nucleus within the indirect basal ganglia pathway. However, a subpopulation of GPe neurons projects directly to the striatum, raising questions about their compartmental and cell-type-specific targeting.

Methods: To address this issue, we employed neural tracing and ex vivo whole-cell patch-clamp recordings with optogenetics using adeno-associated viral vectors in rats. Anatomical observations and intersectional labeling techniques were applied to examine spatial relationships of projections among the striatum, GPe, and ventral thalamus.

Results: GPe axons exhibited a strong bias toward the matrix compartment of the striatum. This biased projection originated from both subthalamic nucleus-targeting and striatum-targeting GPe neurons. In contrast, striatal projections to the GPe arose from both matrix and striosome compartments. Optogenetic stimulation of GPe axons elicited inhibitory postsynaptic currents in medium spiny neurons (MSNs) and cholinergic interneurons (CINs) in the matrix compartment. Cesium-based recordings indicated distal synaptic contacts in MSNs. Anatomical data also revealed proximal appositions of GPe axons to CIN somata and dendrites. Excitatory inputs from motor cortical areas and ventral thalamic nuclei also preferentially targeted the matrix. Furthermore, optogenetic stimulation of ventral thalamic axons elicited excitatory postsynaptic currents in GPe neurons. Intersectional labeling revealed substantial overlap between striatal neurons and axons of GPe neurons, both of which were innervated by the same population of ventral thalamic neurons.

Discussion: These findings suggest that convergent cortical and thalamic excitation of both the striatum and GPe may induce feedforward inhibition within the striatal matrix, particularly onto CINs. This mechanism may contribute to the fine-tuning of striatal output in motor-related basal ganglia circuits.

The anterior retrosplenial cortex (aRSC) functions as a hub that integrates multimodal sensory inputs into associative recognition memories. Although the aRSC receives dense serotonergic projections from the raphe nuclei, the role of serotonin in its function remains poorly understood. Among serotonergic receptors, 5-HT2A receptors (5-HT2ARs) are highly expressed in cortical regions, including the aRSC, and have been implicated in the modulation of cognitive processes. Based on our previous work demonstrating the involvement of the aRSC in recognition memory, here we investigated the contribution of 5-HT2ARs (memory) during different phases of the object recognition (OR) task in rats. We found that selective blockade of 5-HT2ARs in the aRSC differentially affected acquisition, consolidation, and retrieval. These findings identify 5-HT2ARs in the aRSC as critical modulators of recognition memory processing and suggest that their dysregulation could contribute to cognitive impairments observed in conditions such as Alzheimer's disease.

Introduction: Studies indicate that pattern separation for spatial and object information involves structures of the temporal cortex (lateral entorhinal and perirhinal cortices) and hippocampus (dentate gyrus and CA3), which are particularly sensitive to aging. However, little is known about how the hippocampal network, the anteroposterior axis of these regions, and the excitatory-inhibitory circuit contribute to the recognition and separation of object patterns.

Methods: This study investigated the expression of c-Fos and PV along the anteroposterior axis of the hippocampus in a multi-trial task to assess the recognition of novel objects and recognition of novel objects with different levels of similarity. Five groups of animals performed tasks with different similarity demands (NOR, DIST, 25, 50, 75%).

Results: The data showed that conditions of greater similarity led to increased c-Fos expression in CA3c and Hilus in the rostral hippocampus. Graph analysis revealed that hippocampal networks became more densely interconnected and efficient as object similarity increased. Furthermore, different patterns of cluster organization emerged depending on task demands. Besides, the granule cell layer along the dorsoventral axis exhibited greater activation of inhibitory neurons (PV+/c-Fos+) under conditions of higher similarity. Differential inhibitory/excitatory control of the DG-CA3 microcircuit network is seen across conditions. Modeling the DG layers revealed robust control of GCs through direct and indirect effects of interneurons present in the hilus and granule layer. Bidirectional direct and indirect effects of MCs on GCs were observed.

Discussion: These results contribute to our understanding of how brain networks and DG excitatory/inhibitory microcircuits are jointly engaged in object recognition memory and disambiguation of overlapping inputs.