Abstract
The prelimbic cortex (PrL), located in the ventral part of the medial prefrontal cortex (mPFC), collaborates with the basolateral amygdala (BLA) to regulate cognitive functions, particularly in learning and memory. However, it remains unclear whether exposure to deoxynivalenol (DON), a common mycotoxin, disrupts these neural circuits and contributes to cognitive impairments. Our study reveals that DON exposure significantly impairs memory and spatial learning abilities in mice. We found increased connectivity between glutamatergic neurons in the BLA and PrL following DON exposure, indicating its role in memory impairments. Whole-cell patch-clamp recordings demonstrated that DON diminishes excitatory synaptic transmission in the PrL and reduces dendritic complexity and spine density. Notably, activation of BLA-PrL glutamatergic projections alleviated memory impairment induced by DON. Furthermore, our research utilized spatial metabolomics analysis to identify potential intervention targets, specifically Sphingomyelin Synthase 2 (SMS2), that could mitigate the adverse effects of DON on cognitive health by modulating sphingomyelin levels. This study enhances our understanding of the neurobiological mechanisms underlying cognitive dysfunction due to DON exposure and provides valuable insights for public health and clinical strategies.