抄録
Although learning induces long-term potentiation in hippocampal area CA1, the molecular and cellular mechanisms underlying learning-dependent plasticity of CA1 pyramidal neurons are still unknown. By combining in vivo gene delivery with in vitro patch-clamp recordings, we found that hippocampal-dependent inhibitory avoidance (IA) learning drives recombinant GluR1, an AMPA receptor subunit, into synapses formed between CA3 and CA1 pyramidal neurons. For the in vivo gene delivery, we used recombinant Herpes virus injected into the dorsal hippocampus of male rats at 4 weeks of age. The brain was sliced 30 min after the IA training, and infected neurons were identified by the GFP tag on GluR1. Moreover, IA learning significantly increased AMPA/NMDA ratio suggesting synaptic delivery of endogenous AMPA receptors. For the behavioral study, recombinant Herpes virus were bilaterally injected into the dorsal hippocampus to express the GluR1 cytoplasmic tail in CA1 pyramidal neurons, a construct that inhibits synaptic delivery of endogenous AMPA receptors during long-term potentiation in vitro and experience in vivo. The expression of GluR1 cytoplasmic tail successfully impaired the IA learning performance without changing the latency to enter the novel dark box or the amount of 24-hour spontaneous locomotor activity. These results show that synaptic delivery of AMPA receptors into Shaffer collateral synapses plays an essential role in hippocampal-dependent learning function in behaving rats. [J Physiol Sci. 2008;58 Suppl:S142]
