Postsynaptic Expression of a New Calcium Pathway in Hippocampal CA3 Neurons and its Influence on Mossy Fiber Long-Term Potentiation

Abstract

Long-term potentiation (LTP) in the CA1 region of the hippocampus is induced by postsynaptic Ca2+ influx via NMDA receptors (NMDARs). However, this synaptic plasticity occurs independently of NMDARs when Ca 2+-permeable AMPA receptors (AMPARs) are expressed at postsynaptic sites using various genetic techniques, indicating that an increase in Ca 2+ level at critical postsynaptic sites, regardless of its entry pathway, triggers the induction of LTP at CA1 synapses. In contrast, NMDARs are sparsely distributed on mossy fiber (MF) synapses in CA3 hippocampal neurons, and most evidence favors the presynaptic mechanism for LTP induction, although some reports suggested a postsynaptic mechanism. In this study, we examined whether Ca2+ influx through the newly produced postsynaptic receptors during high-frequency stimulation affects the induction of MF LTR For this purpose, we expressed Ca2+-permeable AMPARs in CA3 pyramidal neurons by Sindbis viral-mediated gene transfer of the unedited form of the glutamate receptor 2 (GluR2Q) subunit, as a new pathway for postsynaptic Ca 2+ entry, in rat hippocampal organotypic cultures. Virally expressed myc-tagged GluR2Q was detected at the complex spines known as the thorny excrescences, which serve as postsynaptic targets for MF synaptic input, on the proximal apical dendrites of CA3 pyramidal cells. Furthermore, endogenous Ca2+-impermeable AMPARs at MF synapses were converted into Ca 2+-permeable receptors by GluR2Q expression. However, the postsynaptic expression of Ca2+-permeable AMPARs had no significant influence on the two types of MF LTP induced by different stimulus protocols. These results supported the notion that MF LTP is independent of postsynaptic Ca2+.