Shavit-Stein Efrat, Artan-Furman Avital, Feingold Ekaterina, Ben Shimon Marina, Itzekson-Hayosh Zeev, Chapman Joab, Vlachos Andreas, Maggio Nicola
Department of Neurology, The Chaim Sheba Medical Center Tel HaShomer, Israel.
Department of Neurology, The Chaim Sheba Medical CenterTel HaShomer, Israel; Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel Aviv UniversityTel Aviv, Israel.
Front Mol Neurosci. 2017 Mar 2;10:42. doi: 10.3389/fnmol.2017.00042. eCollection 2017.
Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of -methyl-D-aspartate receptors. These results demonstrate that the effects of PAR2 on synaptic plasticity are distinct from what is observed upon PAR1-activation. Thus, we propose that the activation of different classes of PARs, i.e., PAR1 and PAR2, may set the threshold of synaptic plasticity in the hippocampal network by balancing LTP and LTD.
蛋白酶激活受体（PARs）参与调节大脑中的突触传递和可塑性。虽然人们普遍认为PAR1介导兴奋性突触强度的长期增强（LTP），但PAR2在突触可塑性中的作用仍未得到充分理解。在本研究中，我们评估了PAR2信号在海马体沙费尔侧支 - CA1突触可塑性中的作用。通过场电位记录，我们报告PAR2激活通过蛋白激酶A依赖性、瞬时受体电位香草酸亚型4介导的机制导致突触传递的长期抑制（LTD），这需要N - 甲基 - D - 天冬氨酸受体的激活。这些结果表明PAR2对突触可塑性的影响与PAR1激活时所观察到的不同。因此，我们提出激活不同类别的PARs，即PAR1和PAR2，可能通过平衡LTP和LTD来设定海马体网络中突触可塑性的阈值。
