Multifactorial neural disruption in the brain of the Senegalese sole (Solea senegalensis) under ocean acidification

Global ocean acidification, driven by rising atmospheric CO₂, threatens marine ecosystems and biodiversity, with increasing evidence of disruptive effects on fish neurobiology and behaviour. However, the precise mechanisms underlying these impacts remain largely unresolved.Here, we reveal how chronic exposure to future-predicted CO₂ levels disrupts brain function in the marine teleost Solea senegalensis. Using an integrative approach combining electrophysiology, immunohistochemistry and transcriptomics, we demonstrate that elevated CO₂ induce a complex multifaceted disruption in brain physiology. Contrary to the prevailing GABA_A receptor reversal hypothesis, which predicts Cl^- loss and heightened excitatory signalling under high CO₂, we observed increased Cl^- and HCO₃^- in cerebrospinal fluid and suppressed neural excitability. Immunohistochemistry revealed reduced expression of glial fibrillary acidic protein across multiple brain regions, suggesting glial impairment. Furthermore, transcriptomic profiling of the olfactory bulb uncovered immune modulation, downregulation of neural excitability genes, and upregulation of neuroplasticity, ciliary, and anti-inflammatory pathways, hallmarks of cellular stress adaptation. Notably, genes involved in circadian regulation and thyroid signalling were also dysregulated, pointing to broader neuroendocrine disruption. These findings challenge simplistic models of ocean acidification impact, unveiling a cascading interplay of enhanced GABAergic inhibition, immune shifts, glial dysfunction, and disrupted timekeeping mechanisms, likely contributing to the behavioural impairments under high CO₂. Unlike prior studies relying on behavioural assays or direct physiological proxies, our integrative approach, combining direct cerebrospinal fluid ionic measurements, electrophysiology, immunohistochemistry and transcriptomics, unveils a multifactorial physiological cascade. Our work advocated for integrative neurophysiological frameworks to predict marine fish resilience and vulnerability in a rapidly changing ocean.