Dept. of Integrative Biology and Pharmacology, University of Texas Medical School, Houston, TX 77030, USA.
J Neurophysiol. 2010 Mar;103(3):1283-94. doi: 10.1152/jn.00704.2009. Epub 2009 Dec 30.
Activity-dependent alterations of synaptic transmission important for learning and memory are often induced by Ca(2+) signals generated by depolarization. While it is widely assumed that Ca(2+) is the essential transducer of depolarization into cellular plasticity, little effort has been made to test whether Ca(2+)-independent responses to depolarization might also induce memory-like alterations. It was recently discovered that peripheral axons of nociceptive sensory neurons in Aplysia display long-lasting hyperexcitability triggered by conditioning depolarization in the absence of Ca(2+) entry (using nominally Ca(2+)-free solutions containing EGTA, "0Ca/EGTA") or the absence of detectable Ca(2+) transients (adding BAPTA-AM, "0Ca/EGTA/BAPTA-AM"). The current study reports that depolarization of central ganglia to approximately 0 mV for 2 min in these same solutions induced hyperexcitability lasting >1 h in sensory neuron processes near their synapses onto motor neurons. Furthermore, conditioning depolarization in these solutions produced a 2.5-fold increase in excitatory postsynaptic potential (EPSP) amplitude 1-3 h afterward despite a drop in motor neuron input resistance. Depolarization in 0 Ca/EGTA produced long-term potentiation (LTP) of the EPSP lasting > or = 1 days without changing postsynaptic input resistance. When re-exposed to extracellular Ca(2+) during synaptic tests, prior exposure to 0Ca/EGTA or to 0Ca/EGTA/BAPTA-AM decreased sensory neuron survival. However, differential effects on neuronal health are unlikely to explain the observed potentiation because conditioning depolarization in these solutions did not alter survival rates. These findings suggest that unrecognized Ca(2+)-independent signals can transduce depolarization into long-lasting synaptic potentiation, perhaps contributing to persistent synaptic alterations following large, sustained depolarizations that occur during learning, neural injury, or seizures.
活动依赖性的突触传递改变对于学习和记忆很重要，通常是由去极化产生的 Ca(2+)信号诱导的。虽然人们普遍认为 Ca(2+)是将去极化转化为细胞可塑性的必要递质，但很少有人努力测试去极化的 Ca(2+)非依赖性反应是否也能诱导类似记忆的改变。最近发现，海兔伤害感受神经元的外周轴突在没有 Ca(2+)内流（使用含有 EGTA 的名义上无 Ca(2+)溶液，“0Ca/EGTA”）或没有可检测到的 Ca(2+)瞬变（添加 BAPTA-AM，“0Ca/EGTA/BAPTA-AM”）的条件去极化时，会触发长时间的超兴奋性。目前的研究报告称，在这些相同的溶液中，将中枢神经节去极化至约 0 mV 持续 2 分钟，会在靠近其与运动神经元突触的感觉神经元过程中诱导持续>1 小时的超兴奋性。此外，尽管运动神经元输入电阻下降，但在这些溶液中进行条件去极化会在 1-3 小时后使兴奋性突触后电位（EPSP）幅度增加 2.5 倍。在 0 Ca/EGTA 中去极化会产生持续> = 1 天的 EPSP 长时程增强（LTP），而不改变突触后输入电阻。在突触测试中重新暴露于细胞外 Ca(2+)时，先前暴露于 0Ca/EGTA 或 0Ca/EGTA/BAPTA-AM 会降低感觉神经元的存活率。然而，对神经元健康的差异影响不太可能解释观察到的增强，因为这些溶液中的条件去极化不会改变存活率。这些发现表明，未被识别的 Ca(2+)非依赖性信号可以将去极化转化为持久的突触增强，这可能有助于在学习、神经损伤或癫痫发作期间发生的大的、持续的去极化后产生持久的突触改变。
