Zhou Lian, Baxter Douglas A, Byrne John H
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas
J Neurophysiol. 2014 Oct 15;112(8):1936-49. doi: 10.1152/jn.00577.2013. Epub 2014 Jul 16.
Aplysia sensorimotor synapses provide a useful model system for analyzing molecular processes that contribute to heterosynaptic plasticity. For example, previous studies demonstrated that multiple kinase cascades contribute to serotonin (5-HT)-induced short-term synaptic facilitation (STF), including protein kinase A (PKA) and protein kinase C (PKC). Moreover, the contribution of each kinase is believed to depend on the state of the synapse (e.g., depressed or nondepressed) and the time after application of 5-HT. Here, a previously unappreciated role for PKC-dependent processes was revealed to underlie the maintenance of STF at relatively nondepressed synapses. This PKC dependence was revealed when the synapse was stimulated repeatedly after application of 5-HT. The contributions of the PKA and PKC pathways were examined by blocking adenylyl cyclase-coupled 5-HT receptors with methiothepin and by blocking PKC with chelerythrine. STF was assessed 20 s after 5-HT application. The effects of PKC were consistent with enhanced mobilization of transmitter, as assessed by application of hypertonic sucrose solutions to measure the readily releasable pool of vesicles and recovery of the readily releasable pool after depletion. A computational model of transmitter release demonstrated that a PKC-dependent mobilization process was sufficient to explain the maintenance of STF at nondepressed synapses and the facilitation of depressed synapses.
海兔的感觉运动突触为分析促成异突触可塑性的分子过程提供了一个有用的模型系统。例如，先前的研究表明，多种激酶级联反应参与了5-羟色胺（5-HT）诱导的短期突触易化（STF），包括蛋白激酶A（PKA）和蛋白激酶C（PKC）。此外，据信每种激酶的作用取决于突触的状态（例如，抑制或未抑制）以及应用5-HT后的时间。在此，PKC依赖性过程在维持相对未抑制突触处的STF方面的一个先前未被认识到的作用被揭示出来。当在应用5-HT后反复刺激突触时，这种对PKC的依赖性就显现出来了。通过用美噻吨阻断腺苷酸环化酶偶联的5-HT受体以及用白屈菜红碱阻断PKC来研究PKA和PKC途径的作用。在应用5-HT后20秒评估STF。通过应用高渗蔗糖溶液来测量囊泡的易释放池以及耗尽后易释放池的恢复情况来评估，PKC的作用与递质动员增强一致。递质释放的计算模型表明，PKC依赖性动员过程足以解释未抑制突触处STF的维持以及抑制突触的易化。
