The neural architecture of arousal and wakefulness emerges from the coordinated activity of at least six chemically distinct neuromodulatory systems - histaminergic, cholinergic, noradrenergic, dopaminergic, serotonergic, and orexinergic - whose functional differentiation and mutual interdependence resist reduction to any single hierarchical command structure. The default pedagogical approach to arousal systems falls into a classic structural trap: it dismantles a deeply integrated network into an inventory of isolated neurotransmitters. By optimizing the curriculum for taxonomic convenience, this method trades any real understanding of the system's operational mechanics for the illusion of a well-ordered list. The present article formalizes and extends the Chicken Coop Theory (CCT), a structured functional allegory developed within a physiology teaching framework, as a pedagogically and epistemically rigorous model for the integrated teaching of arousal neurobiology, state-space dynamics, and clinical psychopharmacology. Each allegorical role is grounded in mechanistic neuroanatomy, receptor pharmacology, and systems-level evidence. The model generates testable clinical predictions across six canonical pathological scenarios. Each failure-mode scenario corresponds directly to a mechanistically specified neuromodulatory displacement, yielding pharmacological reasoning that aligns with the distributed, non-hierarchical nature of arousal regulation. The CCT constitutes not a simplification of consciousness architecture but a compressed formal map whose internal logic preserves the mechanistic topology of the system it represents - a distinction with direct consequences for how we train clinicians and design pharmacological interventions. The model occupies a productive middle register between monoamine reductionism and computationally demanding psychiatric models, and is applicable across a range of health professions education settings.
The zebrafish (Danio rerio) has emerged as a valuable model system in neuroscience due to their genetic tractability, conserved neuroanatomy, sensitivity to pharmacological manipulations, and suitability for high-throughput screening. Among the many applications of zebrafish in neurobiology, the investigation of glutamatergic (glutamate-based) and GABAergic (gamma-aminobutyric acid-based) signaling has gained increasing relevance, as these two neurotransmitter systems maintain the critical excitatory-inhibitory balance crucial for normal brain function. Dysregulation of this balance underlies a range of psychiatric and neurological disorders, such as epilepsy and seizure disorders, schizophrenia, anxiety-related disorders, and autism spectrum disorders. Zebrafish models demonstrate conserved receptor subtypes and behavioral phenotypes paralleling human conditions, as well as predictable responses to clinically relevant drugs, such as N-methyl-D-aspartate (NMDA) receptor antagonists, GABA agonists, and anticonvulsants. In this review, we integrate these findings to highlight how zebrafish research has contributed to understanding glutamate and GABA pathway dynamics at molecular, cellular, and behavioral levels. We critically outline experimental strategies used to model these pathologies in zebrafish and summarize key genetic, biochemical, and behavioral endpoints for assessing neurotransmitter function. Finally, we discuss current limitations and propose future directions to enhance the translational impact of zebrafish models in neuropsychiatric research.
The dorsolateral column of the periaqueductal gray (dPAG) is a midbrain structure involved in innate defensive reactions but also contributes to processes relevant to the neurobiology of post-traumatic stress disorder (PTSD). However, whether dPAG activity contributes to the expression and consolidation of aversive memories, as well as persistent anxiety-like states, remains unclear. The present study investigated these processes in male and female Wistar rats using the conditioned place aversion (CPA) paradigm followed by the elevated plus maze (EPM) test to assess anxiety-like behavior. Chemical stimulation of the dPAG with N-methyl-D-aspartate (NMDA) served as the unconditioned stimulus, whereas functional inactivation was achieved by microinjection of cobalt chloride (CoCl2), a non-specific synaptic blocker. Inactivation was performed 1 h before the CPA test to evaluate memory expression or 1 h before the EPM test to assess anxiety-like state. In a separate experiment, the protein synthesis inhibitor anisomycin (ANS) was administered into the dPAG after conditioning to examine memory consolidation. NMDA stimulation induced robust CPA and increased anxiety-like behavior. Inactivation of the dPAG before the CPA test impaired CPA expression without altering the anxiety-like phenotype in the EPM. In contrast, inactivation before EPM exposure prevented this anxiety-like response. ANS administration impaired CPA consolidation and prevented the anxiety-like phenotype. These findings implicate the dPAG from male and female rats as a key brain area involved in the expression and consolidation of aversive memories, as well as in the development of anxiety-like states, at least when it is recruited during the aversive event.
Until recently, slow waves (SWs) were considered to be highly specific, if not exclusive, to sleep and non-rapid eye movement (NREM) sleep in particular. During NREM sleep, they are proposed to track and contribute to normalization of homeostatic sleep pressure. However, recent evidence has identified typical SWs during wakefulness and rapid-eye movement (REM) sleep. SWs during wakefulness have been regarded as intrusions of sleep, supported by the finding of an associated down-state of neural activity. Although this suggests that the underlying neurobiology of SWs might be shared across vigilance states, i.e. the activity of neurons is comparable, it does not address the question as to whether SWs display state-dependent differences that could reflect a homeostatic regulation. To address this question, we utilized an intracranial dataset of 106 adult patients with drug-resistant epilepsy and computed specific features of SWs-their incidence, slope, transition frequency, associated high gamma activity, multipeak morphology and overlap across brain regions. Overall, we found that changes in these features reflect a state-dependent modulation, potentially in line with expected changes in homeostatic pressure. The multipeak morphology displayed the greatest changes across states. SW differences were sufficiently specific to vigilance state that we could successfully classify these states using SW properties. Our work provides further evidence that SWs during wakefulness and REM sleep are consistent with intrusion of NREM-SW and establish normative values for future studies on SWs across vigilance states and brain regions.
Fast gait training, individually and when combined with functional electrical stimulation (FastFES), has been shown to improve walking function in individuals post stroke. However, the neural mechanisms underlying the effects of these two gait training interventions are poorly understood. The purpose of this mechanism-focused gait rehabilitation randomized clinical trial is to assess the effects of Fast and FastFES gait training interventions on corticospinal neurophysiology, gait biomechanics, energy cost, and walking function in individuals with chronic post-stroke hemiparesis. In this randomized clinical trial, participants with chronic stroke are recruited and randomized to receive one of two gait training interventions-FastFES or Fast. Participants in each intervention group receive 12 sessions of gait training, with each training session comprising 30 min of training. During FastFES training, electrical stimulation is delivered to ankle dorsi- and plantar-flexor muscles during paretic swing phase and late stance phase, respectively. Evaluations of clinical, gait biomechanics, neurophysiological, and energy cost outcomes are performed at baseline, after completion of 12 training session (post12), and at 3-weeks and 6-weeks after completion of training (3-week follow up, 6-week follow up), to measure longitudinal effects of gait training. Additional evaluations are performed at completion of 3 and 6 training sessions (post3 and post6) to measure the time course of change during gait training. Upon completion of the study, planned analyses will include between-group comparisons of FastFES versus Fast gait training on training-induced changes in corticomotor and spinal excitability, gait biomechanics outcomes such as peak anterior ground reaction force, as well as association of training-induced changes in corticospinal neurophysiology and gait biomechanics with clinical and energy cost measures. By elucidating the biomechanical and neural correlates underlying gait training-induced changes in locomotor function, this study promises to build on existing evidence supporting the clinical effects of FastFES and Fast gait training. The long-term goal of this study is to inform the development of neurobiology-informed, personalized, and innovative strategies to enhance the effectiveness of stroke gait rehabilitation. clinicaltrials.gov, identifier NCT04380454.
This cross-sectional study investigates the global incidence of pediatric central nervous system tumors in 2022.
KIF1A-associated neurological disorder (KAND) encompasses a broad neurodevelopmental and neurodegenerative spectrum in which motor and movement disorders are common but incompletely defined. To systematically characterize motor and movement disorder phenotypes in KAND. In this cross-sectional study, 51 individuals with likely-pathogenic or pathogenic KIF1A variants underwent standardized neurological assessment using the Spastic Paraplegia Rating Scale (SPRS), SPATAX disability scale, Gross Motor Function Classification System (GMFCS), and Modified Ashworth Scale. A history of global developmental delay was present in 96.1% and neonatal or infantile hypotonia in 62.7%. Progressive spasticity occurred in 72.5%, predominantly affecting the lower extremities and correlated with age (β = 0.45, odds ratio [OR] = 1.56, 95% confidence intervals [95% CI] 1.09-2.25, P = 0.016). Lower extremity weakness was nearly universal (88.2%) and inversely related with age (β = -0.08, OR = 0.93, 95% CI 0.86-0.99, P = 0.032). Independent walking was achieved by 62.7% at a median age of 24 months, but only 31.4% retained independent ambulation at last evaluation. Movement disorders included motor stereotypies (43.1%), ataxia (19.6%), action tremor (15.6%), and dystonia (3.9%). Cerebellar signs were present in 37.2%. The p.Glu253Lys variant was associated with the most severe phenotype. KAND encompasses a continuous spectrum of motor and movement disorders that integrates developmental and neurodegenerative features. These findings inform clinical management, genetic counseling, and the design of future clinical trials. © 2026 International Parkinson and Movement Disorder Society.
Extracellular vesicles (EVs) mediate intercellular communication by transferring bioactive molecular cargo. We present a protocol for isolating EVs from fibroblast growth factor-2 (FGF2)-primed primary mouse astrocytes using differential ultracentrifugation. We describe steps for primary astrocyte culture, FGF2 priming, EV isolation, and comprehensive characterization encompassing transmission electron microscopy (TEM). We then detail procedures for nanoparticle tracking analysis (NTA), western blotting, and mass spectrometry-based proteomic analysis. EVs isolated by this approach protect against mitochondrial and synaptic toxicity in Parkinson's disease models. For complete details on the use and execution of this protocol, please refer to Wen et al.1.
Whether auditory perception can be non-invasively induced by optical stimulation without genetic modification remains an open question in sensory neuroscience and neuroprostheses. This study presents the first demonstration that transtympanic infrared laser stimulation of the cochlea evokes reliable auditory-guided behavior in awake animals. Mongolian gerbils (Meriones unguiculatus) were subjected to classical conditioning where a reward water delivery was predicted by either cochlear laser stimulation or sound stimulus. Laser-conditioned animals successfully learned licking behavior, with conditioned responses and behavioral properties comparable to auditory-conditioned animals. The laser-evoked response was significantly inhibited by auditory masking, and auditory-conditioned animals demonstrated stimulus generalization to laser stimulation. These findings provide behavioral-level evidence that transtympanic infrared laser stimulation can evoke an auditory percept. Our work establishes a foundation for exploring contactless optical stimulation as a non-invasive strategy for engaging the auditory periphery and informs future development of optical approaches to auditory prosthetic technologies.
Autism spectrum disorder (ASD) is highly heritable; however, the neural architecture underlying semantic processing and social functioning, and the extent to which it reflects familial liability, remains insufficiently understood. Unaffected siblings (SIB), who share substantial genetic liability with individuals with ASD, offer a critical framework for identifying intermediate neural phenotypes. We examined 36 individuals with ASD, 36 SIB, and 37 typically developing (TD) controls, matched for age, IQ, and handedness. Functional magnetic resonance imaging (fMRI) during a semantic judgment task was used to compare neural activation across groups and to assess whether associations with social functioning, measured by the Social Responsiveness Scale (SRS), reflected familial risk or dimensional continuity across the autism spectrum. Group comparisons revealed a graded endophenotypic pattern in inferior frontal gyrus (IFG) activation, with reduced activation in ASD and intermediate responses in SIB. The middle temporal gyrus (MTG) showed a similar but weaker gradient, with SIB not differing significantly from TD. Both ASD and SIB also demonstrated heightened cuneus activation, consistent with a heritable compensatory shift toward perceptual processing. Importantly, reduced MTG activation, along with a weaker marginal pattern in the IFG, was associated with higher SRS scores in both the familial and full samples, suggesting an association between semantic activation and social functioning. These findings clarify how familial liability and dimensional variation jointly shape the neural organization of semantic processing and social functioning in ASD.
Poisonings are a global public health challenge, especially for older adults with dementia. This study examined the incidence, types and medications involved at the time of poisoning among older people with and without dementia in Sweden. Using linked Swedish national registries, we conducted a matched cohort study of individuals ≥65 years with dementia diagnosed between 2014 and 2018, matched 1:3 to controls by age and sex, and followed until December 2019. Poisonings were identified via International Classification of Disease-10 codes. Incidence rates (IR) and hazard ratios (HR) were estimated using survival models. Among 415 016 participants, dementia was associated with higher poisoning incidence (IR 100.3 vs 76.4 per 100 000 person-months; HR at 6 months 1.48). Risks were greatest for unintentional poisonings, toxic pharmaceutical effects and adverse drug reactions within 6 months postdiagnosis. Psychotropics, antithrombotics and cardiovascular medications were the most commonly used. Dementia is associated with poisoning risk, warranting cautious prescribing and prevention strategies.
Maternal inflammatory response (MIR) during early mouse gestation induces a cascade of physiological and behavioral changes associated with autism spectrum disorder (ASD). We have shown that mild MIR causes chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth with regionally specific volumetric changes, sensory processing dysregulation, and repetitive behavior abnormalities. Prior rapamycin studies in autism models focused on chronic treatments that alter or prevent physical brain changes. Here, we focus on acute rapamycin effects to uncover novel mTOR pathway-mediated mechanisms of dysfunction. Within 2 hours, rapamycin rescues neuronal hyperexcitability, seizure susceptibility, functional network connectivity, brain community structure, repetitive behaviors, and sensory over-responsivity in adult MIR offspring. These CNS-mediated effects coincide with altered expression of genes associated with ASD, ion channels, and epilepsy. Our findings demonstrate that mTOR dysregulation drives dysfunctional brain development in MIR offspring but the adult brain remains amenable to rapid functional normalization, rescuing core and comorbid ASD-associated brain and behavior phenotypes. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing multiple ASD phenotypes.
Traumatic brain injury (TBI) involves complex secondary injury cascades in which neuroinflammation is a prominent driver. The lack of standardized models capturing a spectrum of injury severities has hindered a systematic understanding of the associated cellular and molecular responses. This study aims to systematically characterize the dynamic responses and phenotypic shifts of neurons, microglia, and astrocytes during the acute and subacute phases following TBI of varying severities. By integrating macroscopic histopathological assessments with microscopic cellular analyses and correlating these with early peripheral biomarker changes, we seek to provide a solid experimental foundation for understanding TBI mechanisms and developing severity-stratified diagnostic and therapeutic strategies. Male mice were randomly assigned using a computer-generated randomization sequence to the following experimental groups: Sham group, mice that underwent only craniotomy (n = 10 per group); Mild group, mice with a 0.5 mm depth impact on the right motor cortex (n = 10 per group); Moderate group, mice with a 1.0 mm depth impact on the right motor cortex (n = 10 per group); Severe group, mice with a 2.0 mm depth impact on the right motor cortex (n = 10 per group). On Days 1, 3, 7, and 14 after injury, tissue damage was assessed using Nissl staining; anxiety-like behavior was evaluated using the elevated plus maze; cognitive function was assessed using the Y-maze test; motor function was evaluated using the open field test, balance beam test, rotarod test, and gait analysis; neuronal apoptosis and glial cell polarization levels were assessed using immunofluorescence staining; and changes in peripheral serum markers were measured using enzyme-linked immunosorbent assay (Elisa). In addition, severely injured mice received minocycline treatment (45 mg/kg, n = 12 per group) from 30 min to Day 3 post-injury, while the control group received the same volume of saline. For comparisons between groups at a single time point, one-way analysis of variance (ANOVA) followed by Tukey's multiple comparisons test was used. For comparisons between groups across multiple time points, two-way ANOVA followed by Tukey's multiple comparisons test was applied. Impact depth was directly correlated with histopathological lesion volume and dictated the trajectory of functional recovery. Motor deficits and neuronal apoptosis scaled with injury severity. The neuroimmune response was severity-dependent: mild TBI triggered a transient, reparative response dominated by M2 microglia and A2 astrocytes. In contrast, severe TBI provoked an early and sustained pro-inflammatory state, characterized by persistent M1 microglial and neurotoxic A1 astrocytic activation (n = 4 per group, p < 0.0001). Furthermore, severe injury led to significant acute elevations in serum interleukin-6 (IL-6) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) within 6 h post-injury (n = 3 per group, p < 0.0001). Minocycline treatment attenuated neuroinflammation, improved motor function, and promoted a shift in microglial polarization toward the protective M2 phenotype (n > 4 per group, all p < 0.05). Our findings establish that TBI severity is a critical determinant of the post-injury neuroimmune microenvironment, with severe injuries driving a maladaptive, chronic inflammatory response. This graded model provides a robust framework for identifying severity-specific biomarkers and validates the rationale for developing precision immunomodulatory therapies stratified by injury severity.
Spermatogenesis, the complex developmental process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of divisions. The basic physiological principles, however, that control seminiferous tubule function remain poorly, if at all, defined. Here, we address cell type-specific seminiferous tubule signaling in vitro and in vivo. By monitoring changes in cellular Ca2+ concentration at high spatiotemporal resolution, we show that the three cell types that build the seminiferous epithelium-Sertoli, peritubular, and germ cells-each display unique Ca2+ signaling patterns. We reveal the underlying mechanisms and demonstrate that Sertoli cell Ca2+ signals are under gonadotropin regulation. Together, our experimental findings provide insights into seminiferous tubule signaling, its mechanistic basis, and its endocrine control.
Activity-induced Long-Term Potentiation (LTP)-characterized as it is by rapid induction, synapse specificity, and remarkable persistence-has long been considered a primary substrate for memory encoding. There has however been considerable debate about the cellular mechanisms responsible for producing the potentiated state. It seems that much of the confusion can be traced to an implicit assumption that there is a single form of stable potentiation. However, features of LTP in Schaffer-commissural (SC) input to CA1 and perforant path projections from entorhinal cortex to dentate gyrus (DG), show that different nodes of the hippocampal circuit express different types of LTP and that distinctions can be found even within the same population of synapses. For the SC system, brief theta burst stimulation (TBS) elicits LTP that is expressed by an expansion of the spine, postsynaptic density and associated AMPA receptor pool, and stabilized by reorganization of the actin cytoskeleton. Both sexes employ these mechanisms but females rely on locally synthesized estrogen and synaptic estrogen receptors to set processes in motion whereas males more heavily rely on metabotropic NMDA receptor signaling. Extended theta burst trains, high frequency stimulation (HFS), and spike timing paradigms engage mechanisms of LTP induction that differ from those produced by the minimal TBS. And an even more radical form of potentiation is expressed at lateral perforant path (LPP) connections with the DG. In this case, LTP is triggered postsynaptically but expressed presynaptically by increased transmitter release with an endocannabinoid providing the requisite retrograde messenger. These sex- and region-specific differences in plasticity have meaningful consequences for episodic memory encoding and vulnerability to neurological insults.
The common marmoset is rapidly emerging as a powerful nonhuman primate model in neuroscience, yet the development of scalable, mechanistically informative cognitive paradigms has lagged behind advances in neural recording and genetic tools. Here, we introduce and validate a touchscreen-based spatial working memory task designed for direct cross-species translation between marmosets and humans. The paradigm independently manipulates retention delay and spatial separation between test choice stimuli, enabling parametric control over maintenance and interference demands within a single framework. Twelve marmosets and seventy-one human participants performed a Delayed Non-Match-to-Position task in which memory delay (1, 5, 10 s) and angular separation between target and distractor locations were systematically varied. Across species, accuracy declined as delay increased and as spatial separation decreased, demonstrating robust sensitivity to both maintenance demands and similarity-based interference. Critically, delay and separation interacted in both species, indicating that these had additive effects. Choice latency analyses further supported interpretation of performance, with slower responses on incorrect trials in both groups. Together, these findings establish a scalable and translationally aligned spatial working memory paradigm that captures interacting maintenance and interference processes. This task provides a powerful platform for circuit-level investigation and offers a sensitive cognitive assay for future studies of aging, neurodegenerative disease, and therapeutic intervention in the marmoset model.
Microglia regulate brain health and disease through diverse, dynamic activation states, but capturing this continuous heterogeneity at scale remains challenging. We developed an imaging and analysis framework to map activation landscapes of human iPSC-derived microglia (iMG) at single-cell resolution. High-content imaging combined a hypothesis-driven immunofluorescence (IF) panel targeting NF-κB, ASC, and CD45 with a discovery-oriented cell painting (CP) assay. Phenotypes were quantified using handcrafted and representation-learning features. To classify cells, we applied Gaussian mixture models (GMMs), enabling soft probabilistic assignments that capture transitional states. Compared with graph-based methods such as Leiden, GMMs achieved similar performance while providing more interpretable descriptions of microglial heterogeneity. Deep-learning features from the targeted IF panel were most informative, yielding high classification accuracy and strong correlation with biological readouts, including NLRP3 inflammasome activation. This platform offers a scalable approach to quantify microglial states and provides a scalable platform for discovering compounds that modulate microglial phenotypes.
The malignant progression of cancer depends not only on oncogenic driver mutations but also on the adaptive rewiring of organelle stress responses that sustain cell survival under hostile tumor microenvironment (TME) conditions. Among these, the hijacking of lysosomal homeostasis has emerged as a critical vulnerability and a driver of therapeutic resistance. Glycoprotein nonmetastatic B (GPNMB), a highly glycosylated type I transmembrane protein predominantly localized to lysosomes, is robustly upregulated across multiple cancer types as an adaptive responder to lysosomal stress. In tumors, GPNMB drives proliferation, metastasis, and immune evasion by engaging multiple oncogenic signaling cascades, while simultaneously shaping an immunosuppressive TME through CD8+ T cell exhaustion and cytokine networks. Clinically, high GPNMB expression correlates with poor prognosis in breast cancer, hepatocellular carcinoma (HCC), lung cancer, glioblastoma (GBM), gastric cancer (GC), and osteosarcoma (OS), positioning it as both a prognostic biomarker and a therapeutic target. The GPNMB-directed antibody-drug conjugate (ADC) glembatumumab vedotin (GV) has demonstrated clinical activity in triple-negative breast cancer (TNBC) and melanoma, yet its efficacy remains constrained by target expression heterogeneity, the reliance on lysosomal trafficking for payload release, and dose-limiting toxicities. Emerging strategies, including bispecific antibodies, immunotoxins, and senolytic elimination of GPNMB-high damaged cells, are expanding the therapeutic landscape. This review dissects the molecular mechanisms, pathological roles, and evolving clinical applications of GPNMB in cancer, highlighting current challenges and future directions for precision oncology.
Patient portals are central to health care communication, yet disparities in adoption persist among underserved populations. Most implementation strategies draw on general population research, but adoption mechanisms may differ substantially in safety-net settings. This mixed-methods cross-sectional study examined portal adoption barriers at a student-run free clinic serving predominantly uninsured, Spanish-speaking adults (n = 112 patients, N = 42 practitioners), with comparison to the Health Information National Trends Survey 6 (n = 5232). Exploratory cluster analysis identified patient engagement patterns. Semistructured interviews (n = 11) contextualized quantitative findings. Logistic regression models compared behavioral predictors across settings. Portal adoption was 22.3% locally vs 66.1% nationally. Cluster analysis identified 4 engagement patterns reflecting distinct barriers, including patients with high health confidence but low information access. Qualitative interviews revealed system usability and trust barriers rather than health literacy deficits. A logistic regression model using behavioral predictors performed well nationally (area under the curve = 0.78) but poorly locally (area under the curve = 0.37), suggesting different adoption mechanisms in safety-net settings. Only 44.3% of practitioners found the portal easy to use. Equitable digital health implementation requires community-specific barrier assessment rather than reliance on generalized national models. System-level usability and trust barriers, rather than individual behavioral deficits, may drive low portal adoption in underserved populations.
Iron accumulations have been identified in resected tissue from patients with refractory temporal lobe epilepsy. These deposits are linked to ferroptosis, a form of nonapoptotic cell death in which iron catalyzes the formation of reactive oxygen species, leading to lipid peroxidation. Experimentally, this process has recently been associated with seizures based on the increased levels of specific markers (4-hydroxynonenal and malondialdehyde) in the brain and plasma. Quantitative susceptibility mapping (QSM) offers an opportunity to detect the iron accumulations in vivo. In this study, we investigated how pilocarpine-induced status epilepticus contributes to the generation of iron deposits in diverse cerebral regions and whether QSM can detect these deposits longitudinally. We scanned 14 animals (n = 10 experimental and n = 4 control) at five different time points (pre-status epilepticus induction and 1, 7, 14, 21 days postinduction) using QSM. We identified iron deposits in the caudate putamen, hippocampus, thalamus, and primary somatosensory cortex of experimental animals, which is consistent with histological findings. The initial size of the hippocampal iron deposits significantly increased over the following weeks. None of these effects was observed in the control animals. The presence of cerebral iron depositions in epilepsy-related brain structures suggests that they could be involved in the onset, development, and progression of spontaneous recurrent seizures. Furthermore, noninvasive, longitudinal in vivo mapping of brain iron deposits could be a potential imaging marker in neurological disorders such as epilepsy. Future experiments will be required to determine the origin of the iron and avoid its progressive accumulation.