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

Abstract

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.

Keywords: Calcium channel; Electron microscopy; Hippocampus; LTP; Synaptic vesicles.