Synaptic ultrastructural alterations in human focal cortical dysplasia: insights from volume electron microscopy

초록

Focal cortical dysplasia (FCD) is a developmental disorder of the cerebral cortex and a leading cause of intractable epilepsy in children. A disrupted excitation-inhibition balance is a hallmark of neuronal hyperexcitability in FCD, yet the underlying ultrastructural mechanisms remain poorly understood. Using volume electron microscopy, we performed a morphological assessment of synapses and organelle distribution in the temporal cortical layer III of an FCD patient. Notably, the dysplastic region displayed fewer excitatory synapses but contained extra-large synapses with more synaptic vesicles. Additionally, inhibitory synapses were located further away from the nearest excitatory synapses, possibly weakening the effectiveness of inhibition in the dysplastic area. There was an increase in mitochondrial density and altered mitochondrial morphology within presynaptic boutons, along with a reduced proportion of postsynaptic protrusions containing a spine apparatus, indicating deficits in intracellular calcium handling and synaptic plasticity. These findings suggest that synaptic architectural modifications may contribute to neuronal hyperexcitability associated with epilepsy in FCD. Keyword: Cortex · Epilepsy · Hyperexcitability · Synapse · Mitochondria