Search Results (1,638)

Motor recovery after stroke, spinal cord injury, or traumatic brain injury reflects relearning rather than simple restitution, as surviving circuits retain plastic potential that can be re-engaged through temporally precise stimulation. This review synthesizes convergent findings demonstrating that Hebbian and spike-timing-dependent mechanisms govern reorganization across cortical, striatal, and spinal levels. Leveraging these timing rules to shape excitability during receptive network states enables durable changes in connectivity and behavior. This effect depends on temporal precision, physiological state, and reinforcement—not stimulus intensity alone—within plasticity windows regulated by metaplastic mechanisms that determine whether Hebbian processes are expressed. Together, these principles define a translational framework for neurorehabilitation, emphasizing biomarker-guided, adaptive, and scalable strategies aligned with intrinsic rules of experience-dependent reorganization. Full article

Type 1 diabetes (T1D) constitutes a chronic metabolic disorder attributed to the autoimmune destruction of insulin-producing pancreatic β cells, which most frequently occurs in childhood. Long-term complications of T1D are expected to occur mainly in adult life, whereas cognitive dysfunction can also occur in children and adolescents with T1D. Most studies demonstrate mild cognitive impairment, especially in the domains of memory, attention and executive functions, all of which affect academic performance, which may also negatively influence adherence to appropriate glucose monitoring and insulin treatment in children and adolescents with T1D. As a result, mild cognitive dysfunction can be an obstacle to both optimal glycemic control during childhood and adolescence and academic achievements for young individuals with T1D. The major metabolic changes occurring around the onset of diabetes, such as severe hyperglycemia and diabetic ketoacidosis, may have a negative impact on brain plasticity during this vulnerable period of neurodevelopment, especially in children diagnosed at a younger age. The pathophysiological mechanisms involved are closely related to increased oxidative stress and the accumulation of advanced glycation end products in the brain, thus leading to neuron cell damage and apoptosis. On the other hand, hypoglycemic episodes and glucose fluctuations may also impair neuronal integrity. The aim of the current narrative review is therefore to present the existing literature data on the clinical aspects, risk factors and molecular mechanisms associated with cognitive dysfunction in children and adolescents with T1D. Full article

Adult neurogenesis, the process of generating new, functional neurons in the mature central nervous system, represents a key mechanism of brain plasticity and a potential source of regeneration. This process occurs primarily within specialised neurogenic niches: the subgranular zone of the hippocampal dentate gyrus (SGZ) and the subependymal zone (SEZ). It is regulated by a complex network of endogenous factors (e.g., hormones, neurotrophins, growth factors) and exogenous factors (environment, stress, diet, physical activity). Impairments in neurogenesis are linked to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In their course, chronic inflammation, mitochondrial dysfunction, oxidative stress, and the accumulation of pathological proteins (β-amyloid, Tau protein, α-synuclein) create a microenvironment that inhibits the proliferation, differentiation, and survival of new neurons. This results in the exacerbation of cognitive and memory deficits. A review of the literature indicates that modulating neurogenesis through non-pharmacological interventions (e.g., a diet rich in anti-inflammatory compounds, physical exercise) and targeted therapeutic strategies represents a promising, albeit complex, research avenue. The primary challenge remains not only stimulating neuron generation but also ensuring their proper maturation, survival, and functional integration into existing neuronal circuits. A deeper understanding of the molecular and environmental mechanisms regulating adult neurogenesis may open new therapeutic possibilities for slowing the progression of neurodegenerative diseases. Full article

Simulated spiking neural networks have been explored for over a hundred years. Many of these networks are driven by biological considerations and an attempt to simulate brains, but others are used with little biological consideration. This paper gives some history of the development of spiking neural models, their use for modelling biological and cognitive phenomena, and for machine learning. It introduces the current state of the art in computational biological neuron and synapse modelling and plasticity. It introduces and reviews balanced spiking networks and their engineering applications. Spiking networks are also used for machine learning, with the hope that their implementation on neuromorphic hardware will bring energy and time savings. Similarly, neuromorphic hardware can enable massive parallelism, supporting larger spiking networks. The use of spiking nets for machine learning, both with biologically plausible models and without, is discussed, showing that effective models already exist. The paper concludes with some notes about implementing spiking nets and a discussion including open questions and future work. Full article

Industrialization has caused extensive environmental change, including a global surge in plastic production and pollution. This has resulted in the accumulation of microplastics (MPs; <5 mm) and nanoplastics (NPs; <1 μm) in ecosystems worldwide. MPs originate from both primary sources, such as cosmetics and industrial applications, and secondary sources, through the degradation of larger plastic debris. As a result, MPs and NPs have become ubiquitous contaminants, posing significant toxicological risks to living organisms. These persistent pollutants are diverse polymers that vary in size, shape, and chemical composition, making their impacts on organism physiology complex and difficult to disentangle. Plastic pollution is particularly severe in aquatic environments, where particles accumulate from terrestrial sources such as urban dust, agricultural runoff, industrial discharges, and wastewater effluents. Although most research has centered on marine ecosystems, emerging evidence indicates that freshwater environments may contain comparable or even higher concentrations of MPs. Once inside the body, MPs can translocate into tissues and exert toxic effects on multiple organ systems. Collectively, plastic pollution poses not only physiological but also neurological and behavioral risks to aquatic life, with potential consequences for ecosystem stability and trophic interactions. Both MPs and NPs are sufficiently small to cross the blood–brain barrier, raising concerns about their potential impacts on the nervous system by interfering with neuronal function and brain development. Plastic particles can accumulate in neural tissues, inducing oxidative stress, neuroinflammation, and disruption of neurotransmitter signaling. Such neurotoxic effects are linked to altered locomotion, feeding, predator avoidance, and social behaviors across multiple species. This review examines current evidence on the neurotoxic effects of plastic pollution in aquatic organisms and underscores the urgent need for further research and action to mitigate its impact. In light of escalating plastic production and inadequate waste management, the growing evidence that MPs and NPs disrupt aquatic nervous systems, behavior, and ecosystem stability underscores an urgent need for intensified research, improved mitigation strategies, particularly for nanoplastics, and the accelerated development of truly safe and sustainable alternatives. Full article

Despite the growing interest in brain structural plasticity and the substantial body of knowledge that has accumulated over recent decades, some issues remain poorly defined, leading to confusion in the interpretation of results. In addition to stem cell-driven neurogenesis in adult neurogenic niches (adult neurogenesis), neuronal precursors in a state of arrested maturation have also been described, representing a form of neurogenesis without division based on so-called “immature” or late-maturing neurons. These processes occur in different brain regions yet share certain molecular markers and temporal windows. Recent advances in comparative neuroplasticity have further complicated our understanding. Studies reveal a reduction in adult neurogenesis in the olfactory bulb and hippocampus of large-brained, gyrencephalic mammals compared with small-brained species such as rodents. Conversely, a higher prevalence of immature neurons has been reported in the neocortex and amygdala of larger-brained mammals. It is becoming evident that evolutionary trade-offs took place in distinct plastic processes, resulting in the predominance of certain forms in particular species, while others coexist and share overlapping markers. Regardless of the approach employed (neuroanatomical, immunocytochemical, phylogenetic, or transcriptional), current evidence indicates substantial heterogeneity in cell types with different origins and fates across diverse mammalian species. These patterns appear to be sculpted by evolutionary pressures yet unified by shared transient maturational states. Full article

Affective disorders, such as major depressive disorder and anxiety disorders, represent a major global health burden, with current treatments proving inadequate for a substantial proportion of patients. Emerging research highlights the microbiota–gut–brain (MGB) axis as a crucial bidirectional communication system influencing brain function and neuroplasticity through neural, endocrine, immune, and metabolic pathways. This narrative review examines probiotics—live beneficial microorganisms—as modulators of adult neurogenesis and synaptic plasticity, two processes fundamentally implicated in the pathophysiology of affective disorders. Preclinical evidence demonstrates that specific strains, particularly from the Lactobacillus and Bifidobacterium genera, promote hippocampal neurogenesis and synaptic function through epigenetic regulation via short-chain fatty acids (SCFAs), notably butyrate-mediated histone deacetylase inhibition, modulation of neuroinflammatory pathways, regulation of neurotransmitter receptor expression across glutamatergic, GABAergic, and monoaminergic systems, and production of neuroactive peptides. Clinical evidence from randomized controlled trials and recent meta-analyses indicates that probiotic supplementation produces significant reductions in depressive and anxiety symptoms, with effects correlating to changes in gut microbiota composition and peripheral neuroplasticity biomarkers, particularly brain-derived neurotrophic factor (BDNF). However, significant methodological limitations persist, including small sample sizes, lack of standardization in probiotic strains and dosages, inconsistent outcome measures, and considerable interindividual variability. While the mechanistic and clinical evidence is biologically plausible and directionally promising, it is not yet sufficient to support definitive therapeutic recommendations. Future research must prioritize adequately powered clinical trials with standardized consortia, comprehensive multi-omics biomarker panels, and precision psychobiotic strategies guided by microbiome-defined patient stratification. Full article

Auditory Brain–Computer Interfaces (BCIs) constitute the vital intervention for profound sensorineural hearing loss where the auditory nerve is compromised, yet their clinical efficacy remains restricted by substantial biological bottlenecks and limited spectral resolution. This review critically examines the evolutionary paradigm of auditory restoration, tracing the transition from static physical replacement to dynamic biological symbiosis. We systematically analyze physiological barriers across cochlear, brainstem, and cortical levels, elucidating how rigid interfaces provoke chronic tissue responses and why linear encoding protocols fail in distorted central tonotopy. The article synthesizes emerging methodologies in material science, demonstrating how soft, bio-integrated electronics and biomimetic topologies effectively address mechanical impedance mismatches. Furthermore, the trajectory of neural encoding is evaluated, highlighting the paradigm shift from traditional envelope extraction to deep learning-driven non-linear mapping and adaptive closed-loop neuromodulation. Finally, the potential of high-resolution modulation techniques, including optogenetics and sonogenetics, alongside AI-facilitated intent perception for active listening, is assessed. It is concluded that future neuroprostheses must evolve into symbiotic systems capable of seamlessly integrating with neural plasticity to enable high-fidelity cognitive reconstruction. Full article

Neural progenitor cell (NPC) transplantation is a promising strategy for spinal cord injury repair, as graft-derived neurons can integrate into host circuitry and promote functional recovery. While the brain-regional and dorsoventral identities of NPCs are known to influence graft composition and performance, the importance of axial (rostrocaudal) identity, specifically whether NPCs must be matched to the spinal level of injury, remains poorly understood. To address this, we compared outcomes following transplantation of NPCs isolated from the anterior embryonic spinal cord (A-NPCs) versus the posterior spinal cord (P-NPCs) in a mouse model of C5 cervical dorsal column injury. Following transplantation, NPCs retained their intrinsic molecular axial identities; P-NPC grafts maintained significantly higher expression of the lumbar-associated gene HoxC10 and possessed a higher proportion of Chx10-high V2a neurons compared to A-NPCs. Despite these maintained molecular differences, A-NPC and P-NPC grafts were indistinguishable in neuronal and glial density, axon outgrowth, and their ability to support host axon regeneration, including the corticospinal tract. Long-term behavioral testing and retrograde transsynaptic tracing revealed no significant differences between groups in the recovery of skilled pellet reaching, grip strength, or synaptic integration with host cervical motor circuitry. These findings demonstrate that although transplanted NPCs retain their molecular axial identity in the adult injured environment, this identity is not a primary determinant of anatomical integration or functional outcome. Our findings suggest a degree of plasticity in graft-host interactions and indicate that strict segment-matching is not essential for the efficacy of NPC-based therapies in spinal cord injury. Full article

Alzheimer’s disease (AD) is a rapidly escalating global health crisis with limited effective treatments. Emerging research underscores the pivotal role of the microbiota–gut–brain axis in AD pathogenesis, prompting the exploration into gut microbiota-targeted interventions. This narrative review aimed to comprehensively synthesize the latest epidemiological, experimental, and clinical evidence regarding the effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics (PPSPs) in AD prevention and management. We conducted a narrative review of relevant literature from the Web of Science and PubMed databases. The search focused on articles published within the last 5 years using keywords such as “Alzheimer’s disease”, “AD”, “gut-brain axis”, “gut microbiota”, “probiotics”, “prebiotics”, “synbiotics”, and “postbiotics”. The findings suggest that PPSPs mitigate AD pathology and improve cognitive performance by modulating gut microbiota, strengthening intestinal barrier integrity, decreasing amyloid-beta (Aβ) deposition and tau hyperphosphorylation, reducing neuroinflammation and oxidative stress, regulating neurotransmitter metabolism, and promoting synaptic plasticity. Some studies also report varied outcomes, attributable to factors like strain specificity, dosage, intervention duration, patient heterogeneity, and methodological differences. In conclusion, targeting the microbiota–gut–brain axis with PPSPs offers a promising, mechanism-based strategy for AD, though further research is essential to optimize specific interventions for clinical application. Full article

Astrocytes are essential gatekeepers of brain homeostasis, and the disruption of their functions can contribute to the development of several neurological diseases. Among astrocyte signaling pathways, the intracellular second messenger Ca²⁺ plays a pivotal role in regulating the release of gliotransmitters, which actively modulate fundamental processes in the brain such as synaptic plasticity and memory function. Several studies over the years support the idea that dysregulated astrocytic Ca²⁺ homeostasis represents a relevant mechanism in Alzheimer’s disease pathogenesis. Early works in transgenic mice modelling Alzheimer’s disease reported increased Ca²⁺ activity in astroglial cells, supporting the idea of hyperactivity as a common trait of astrocytes in this pathology. However, recent studies have described astrocyte Ca²⁺ hypoactivity in various mouse models, revealing a more complex and heterogeneous scenario. In this review, we summarize and critically discuss the main studies addressing the direction(s) of astrocytic Ca²⁺ signaling dysfunction in mouse models of Alzheimer’s disease. We prioritize investigations performed in ex vivo and in vivo conditions, carefully comparing the different experimental approaches used to measure Ca²⁺ activity in astrocytes. By integrating results across multiple mouse models and methodological strategies, we aim to provide a more complete picture of astrocyte Ca²⁺ dysregulation in Alzheimer’s disease. Full article

Hypnosis has traditionally been conceptualized as a clinical technique for reducing physiological symptoms (e.g., pain, nausea) and psychological symptoms (e.g., anxiety, intrusive thoughts), yet emerging neuroscientific evidence suggests it operates through the fundamental mechanisms of emotional regulation and self-integration. This integrative review synthesizes research on clinical hypnosis from cognitive neuroscience, affective science, and clinical practice to examine how hypnotic phenomena modulate large-scale brain networks—particularly the default mode network (DMN), executive control network (ECN), and salience network (SaN)—to reorganize emotional experience and self-referential processing. We propose a formal mechanistic model in which hypnotic induction produces heightened experiential plasticity through coordinated network reconfiguration, enabling adaptive emotion regulation and reduced dissociative fragmentation. Central to this framework is the construct of Fundamental Peace (FP), operationalized as a dynamic neuro-experiential state characterized by: (1) flexible attentional control without effortful suppression; (2) emotional coherence across self-states; (3) reduced self-referential rigidity; (4) compassionate self-awareness. Unlike equanimity (affective neutrality) or well-being (positive evaluation), Fundamental Peace represents integrated regulatory capacity under changing conditions. Key findings from neuroimaging studies demonstrate that hypnotic states consistently reduce DMN activity, enhance ECN-SaN coupling, and modulate connectivity patterns associated with self-referential processing. Meta-analytic evidence from 85 controlled experimental trials shows robust pain reduction effects, while clinical studies document improvements in trauma-related dissociation and emotional dysregulation. We critically evaluate this framework against alternative theories (dissociated control, cold control, predictive processing, social-cognitive models), specify testable predictions, and assess evidence quality across neuroimaging and clinical domains. Implications for trauma treatment, clinical implementation, and future research integrating causal inference methods are discussed, alongside ethical and cultural considerations. Full article

Adult neurogenesis is a regulated form of brain plasticity shaped by interactions between hormonal systems and environmental context. Social experience has been identified as an important modulator of neuronal proliferation, differentiation, and survival across the lifespan, although effects vary across species, developmental stages, and experimental paradigms. This review synthesizes evidence indicating that diverse social behaviors—including isolation, social hierarchy, parenting, sexual interaction, social buffering, and social learning—engage neuroendocrine, neurochemical, and stress-related pathways that are associated with modulation of hippocampal and olfactory neurogenesis. Affiliative and reproductive contexts have been linked in multiple models to enhanced neurogenic indices via gonadal hormones, oxytocinergic and vasopressinergic signaling, and neurotrophic mechanisms, whereas chronic isolation or social defeat has frequently been associated with reduced neurogenic markers, particularly within stress-sensitive regions of the ventral dentate gyrus. Sex differences further shape these patterns, reflecting both biological regulation and uneven sampling across paradigms. Comparative findings in prairie voles, eusocial mole-rats, nonhuman primates, songbirds, and teleost fish indicate that social organization can be accompanied by either increased or constrained neurogenic activity, depending on ecological pressures and life-history strategies. Collectively, the available evidence suggests that adult neurogenesis represents a context-dependent plastic process embedded within vertebrate social systems, while underscoring the need for integrative and evidence-graded interpretations. Full article

Depressive disorders (DDs), especially treatment-resistant depression (TRD), pose a significant challenge worldwide, largely because their underlying biological mechanisms are complicated and treatments often fall short. There is growing evidence pointing to factors like disrupted neuroplasticity, neuroinflammation, irregularities in the hypothalamic–pituitary–adrenal (HPA) axis, and glutamatergic system imbalances as contributors to the onset and persistence of depressive symptoms. Exosomes (small extracellular vesicles involved in communication between cells) have recently gained attention for their potential role in connecting peripheral and central nervous system (CNS) changes. They carry proteins, lipids, and nucleic acids and are even capable of crossing the blood–brain barrier. Because of this, exosomes might provide a window into molecular changes in the brain and serve as accessible biomarkers of disease status and treatment response. Recent research points out that the contents of exosomes, especially microRNAs (miRNAs) and neurotrophic factors like brain-derived neurotrophic factor (BDNF), might play a part in disrupting synaptic plasticity and could be linked to resistance to antidepressants. At the same time, there is growing interest in using engineered exosomes as targeted drug carriers aimed at the CNS. That said, there are still quite a few hurdles to overcome. Methods vary widely between studies, protocols for isolating exosomes are not sufficiently standardized, safety data are limited, and we do not fully understand how drugs and exosomes interact or how they behave pharmacokinetically. This review brings together current findings regarding exosomes in DDs (with particular emphasis on TRD), highlights their promise for diagnosis and treatment, and sets out some of the main questions that need to be answered before clinical application becomes feasible. Full article

Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological conditions. In this study, we investigated the role of HPCA in regulating NMDA receptor expression and function in mouse hippocampal neural precursor cells (mHNPCs). HPCA knockdown significantly reduced the expression of NMDA receptor-related genes, including Grin2C, Shank1, Serpine2, and selectively attenuated NMDA-induced calcium signaling. Transcriptomic analysis identified ELAV-like RNA-binding protein 3 (Elavl3), a neuron-enriched factor associated with neuronal activity, as a downstream candidate affected by HPCA knockdown. Consistently, Elavl3 suppression phenocopied HPCA deficiency, resulting in impaired NMDA receptor activity and reduced neuronal differentiation. Furthermore, hippocampal HPCA knockdown in vivo led to alterations in locomotor activity, contextual memory, and affective behaviors. Taken together, these findings demonstrate that HPCA supports NMDA receptor function and neuronal development, in part through Elavl3-associated pathways, and highlight HPCA as an important regulator of hippocampal function. Full article