Presynaptic increase in IP3 receptor type 1 concentration in the early phase of hippocampal synaptic plasticity

•IP3R1 is associated with presynaptic vesicles.•IP3R1 is expressed in postsynaptic spines.•IP3R1 is increased in the presynaptic terminal after high frequency tetanization.•Presynaptic IP3R1 may be part of early phase synaptic plasticity mechanisms. The inositol 1,4,5-trisphosphate receptor (IP3R) subtype IP3R1 is highly enriched in the brain, including hippocampal neurons. It plays an important function in regulating intracellular calcium concentrations. Residing on the smooth endoplasmic reticulum (sER), the IP3R1 mobilizes calcium into the cytosol upon binding the intracellular signaling molecule IP3, whose concentration is increased by stimulating certain metabotropic glutamate receptors. Increased calcium may mediate synaptic changes occurring during long-term plasticity, which includes molecular mechanisms underlying memory encoding. The exact synaptic localization of IP3R1 in the central nervous system (CNS) remains unclear. We hypothesized that IP3R1, in addition to its known expression in soma and dendritic shafts of hippocampal CA1 pyramidal neurons, also may be present in postsynaptic spines. Moreover, we hypothesized that IP3R1 may be present in presynaptic terminals as well, given the importance of calcium in regulating presynaptic neurotransmitter exocytosis. To test these two hypotheses, we used IP3R1 immunocytochemistry at the light and electron microscopical levels in the CA1 area of the hippocampus. Furthermore, we hypothesized that induction of long-term potentiation (LTP) would be accompanied by an increase in synaptic IP3R1 concentrations, thereby facilitating synaptic mechanisms of long term plasticity. To investigate this, we used quantitative immunogold electron microscopy to determine possible changes in IP3R1 concentration in sub-synaptic compartments before and five minutes after high frequency tetanizations. Firstly, our data confirm localization of IP3R1 in both presynaptic terminals and postsynaptic spines. Secondly, the concentration of IP3R1 after tetanization was significantly increased in the presynaptic compartment, suggesting a presynaptic role of IP3R1 in early phases of synaptic plasticity. It is therefore possible that IP3R1 is involved in modulating neurotransmitter release by regulating calcium homeostasis presynaptically.