Decoding Brain Hyperexcitability Across Disorders: From Molecular Drivers to Circuits and Behavior

Brain function depends on tightly regulated neuronal excitability and balanced excitation–inhibition (E/I) dynamics across molecular, cellular, and circuit levels. When these control systems fail, hyperexcitability can emerge as a convergent mechanism that contributes to symptoms and progression across a wide range of brain disorders—not only epilepsies, but also neurodevelopmental and psychiatric conditions, neurodegeneration and aging-related syndromes, demyelinating disease, and neuroinflammatory/post-infectious states. Despite major advances in identifying ion channels, synaptic proteins, glial regulators, and immune mediators linked to altered excitability, a key challenge remains: connecting molecular drivers to circuit dysfunction and behavior in a way that clarifies causal mechanisms and points to actionable therapeutic strategies.This Research Topic aims to assemble a coherent, mechanism-led collection that decodes brain hyperexcitability across scales, from molecular and cellular determinants to circuit computations and behavioral outcomes. We welcome studies that define how changes in intrinsic membrane properties, synaptic transmission and plasticity, neuromodulatory systems, glial–neuronal interactions (astrocytes, microglia, oligodendrocytes), metabolic and vascular factors, and inflammatory pathways reshape E/I balance and network stability. Contributions that bridge levels of analysis—e.g., linking molecular perturbations to identifiable circuit signatures (oscillations, synchrony, network topology) and to clinically relevant phenotypes—are especially encouraged.The scope is intentionally cross-disorder but not purely descriptive: submissions should retain a clear mechanistic link to excitability/E–I imbalance and explicitly address how the proposed pathway or perturbation produces circuit- and/or behavior-level consequences. We welcome experimental and computational approaches, including multi-omics, single-cell/spatial profiling, advanced electrophysiology, in vivo imaging, causal circuit manipulation, human iPSC-based models, translational biomarkers, and integrative modeling. Studies in animal models and humans are both suitable, including work that identifies therapeutic targets or stratification markers grounded in excitability mechanisms.Suggested themes include (but are not limited to):(• Molecular determinants of altered excitability (ion channels, receptors, transporters, signaling cascades)• Synaptic and homeostatic plasticity mechanisms shaping E/I balance• Glial regulation of neuronal firing and network stability (neurotransmitter clearance, myelination, immune signaling)• Neuroinflammation, infection/post-viral processes, and excitability-mediated circuit dysfunction• Network-level signatures of hyperexcitability (oscillations, synchrony, propagation, criticality) and links to behavior• Cross-disorder comparisons and shared mechanistic pathways with clear disease relevance• Translational biomarkers and mechanism-based interventions targeting excitability and E/I controlArticle types: Original Research, Methods, Hypothesis & Theory, Reviews, and Mini-Reviews that provide mechanistic synthesis and cross-scale integration. Topic editors: Nerea Llamosas, Soraya Martín-Suárez, Marc Tambini Source: https://www.frontiersin.org/research-topics/78345/decoding-brain-hyperexcitability-across-disorders-from-molecular-drivers-to-circuits-and-behavior