Abstract
HPC-1/syntaxin1A is believed to play an important role in the exocytosis of synaptic vesicle. Previously, we have produced HPC-1/syntaxin1A knock-out mouse. In homozygous mutant (KO) mouse, latent inhibition of cued fear memory was attenuated. Surprisingly, the attenuation of latent inhibition in KO mouse was recovered by administration of 5-HT2A-receptor agonist or SSRI, suggesting serotonergic disturbance. In order to examine the effect of 5-HT or cAMP, which is regulated via 5-HT2A-receptor, on hippocampal neurons from KO mouse in vitro, hippocampal slices at 7days in vitro (DIV) and dissociated hippocampal neurons at 14DIV were treated with 5-HT or Sp-cAMPS. Then, they were fixed and immunostained for synaptophysin or synapsin. Among all groups, no difference was observed between wild type (WT) and KO neurons in the number of puncta of synaptophysin in both slice and dissociated cultures. On the other hand, the number of puncta of synapsin in dissociated KO neurons treated with Sp-cAMPS was lower than that in WT neurons. In the 5-HT-applied group, the number of puncta of synapsin was not different between genotypes. Implication of 5-HT signaling and behavioral abnormalities in HPC-1/synataxin1A knock-out mouse will be discussed. [J Physiol Sci. 2008;58 Suppl:S128]
