Elucidation of mechanisms for spontaneous epileptic seizures in mice lacking μ3B, a subunit of the neuron-specific AP-3B complex

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Adaptor protein (AP) complexes regulate the vesicular transport of cargo proteins in the late secretory and endocytic pathways. Mice lacking μ3B, a subunit of the neuron-specific AP-3B complex, suffered from spontaneous epileptic seizures after the age of 15 weeks.In 2003, we performed morphometrical examinations of the CA1 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 2,4,6,8 and 16 weeks. The diameter of synaptic vesicles in excitatory terminals in KO was smaller than that in WT at the ages of 4,6 and 8 weeks, but not at the ages of 2 and 16 weeks. The densities of synaptic vesicles in both terminals in KO were lower than those in WT.In 2004, we performed morphometrical examinations of the CA3 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 4,6,8 and 16 weeks, but not at the age of 2 weeks. On the other, the diameter of synaptic vesicles in mossy fiber terminals in KO was larger than that in WT at the ages of 2-16 weeks. The densities of synaptic vesicles in the mossy fiber terminals, but not the inhibitory, in KO were lower than those in WT.It is possible that the imbalance between excitatory and inhibitory inputs to the hippocampus evokes epileptic seizures in this model.