Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Science, University of Oslo, Oslo, Norway.
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Science, University of Oslo, Oslo, Norway.
Brain Res. 2019 Mar 1;1706:125-134. doi: 10.1016/j.brainres.2018.10.030. Epub 2018 Nov 5.
The inositol 1,4,5-trisphosphate receptor (IPR) subtype IPR1 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 IPR1 mobilizes calcium into the cytosol upon binding the intracellular signaling molecule IP, 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 IPR1 in the central nervous system (CNS) remains unclear. We hypothesized that IPR1, 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 IPR1 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 IPR1 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 IPR1 concentrations, thereby facilitating synaptic mechanisms of long term plasticity. To investigate this, we used quantitative immunogold electron microscopy to determine possible changes in IPR1 concentration in sub-synaptic compartments before and five minutes after high frequency tetanizations. Firstly, our data confirm localization of IPR1 in both presynaptic terminals and postsynaptic spines. Secondly, the concentration of IPR1 after tetanization was significantly increased in the presynaptic compartment, suggesting a presynaptic role of IPR1 in early phases of synaptic plasticity. It is therefore possible that IPR1 is involved in modulating neurotransmitter release by regulating calcium homeostasis presynaptically.
三磷酸肌醇受体（IPR）亚型 IPR1 在大脑中高度丰富，包括海马神经元。它在调节细胞内钙离子浓度方面发挥着重要作用。IPR1 位于光滑内质网（sER）上，当结合细胞内信号分子 IP 时，会将钙动员到细胞质中，而 IP 的浓度会通过刺激某些代谢型谷氨酸受体而增加。增加的钙可能介导长时程可塑性过程中发生的突触变化，包括记忆编码的分子机制。IPR1 在中枢神经系统（CNS）中的确切突触定位尚不清楚。我们假设，除了已知在海马 CA1 锥体神经元的体和树突干中表达外，IPR1 也可能存在于突触后棘中。此外，鉴于钙在调节突触前神经递质胞吐作用中的重要性，我们假设 IPR1 也可能存在于突触前末梢中。为了验证这两个假设，我们在海马 CA1 区使用 IPR1 免疫细胞化学在光镜和电子显微镜水平上进行了研究。此外，我们假设长时程增强（LTP）的诱导伴随着突触 IPR1 浓度的增加，从而促进长时程可塑性的突触机制。为了研究这一点，我们使用定量免疫金电子显微镜来确定高频强直刺激前后亚突触隔室中 IPR1 浓度的可能变化。首先，我们的数据证实了 IPR1 在突触前末梢和突触后棘中的定位。其次，强直刺激后突触前隔室中 IPR1 的浓度显著增加，表明 IPR1 在突触可塑性的早期阶段具有突触前作用。因此，IPR1 可能通过调节钙稳态在突触前参与调节神经递质释放。
