Technion Faculty of Medicine and Network Biology Research Laboratories, Lorry Lokey Center for Life Sciences and Engineering, Technion, Haifa 32000, Israel.
J Neurosci. 2013 Aug 7;33(32):13094-100. doi: 10.1523/JNEUROSCI.2144-13.2013.
Synapses undergo substantial activity-dependent and independent remodeling over time scales of minutes, hours, and days. Presumably, changes in presynaptic properties should be matched by corresponding changes in postsynaptic properties and vice versa. Wherever measured, presynaptic and postsynaptic molecular properties tend to correlate, yet these correlations are often quite imperfect, raising questions as the origins of such mismatches: Are these the outcome of "single snapshot" analyses of asynchronous remodeling processes? Alternatively, do these indicate that synapses genuinely vary in the "stoichiometries" of their presynaptic and postsynaptic molecular contents? If so, are these "stoichiometries" preserved over time? To address these questions, we followed the matching dynamics of the presynaptic active-zone molecule Munc13-1 and the postsynaptic molecule PSD-95 in networks of cultured cortical mouse neurons. We find that presynaptic and postsynaptic remodeling were generally well correlated, but the degree of this correlation was highly variable, with little and even negative correlation observed at some synapses. No evidence was found that remodeling in one compartment consistently preceded remodeling in the other. Interestingly, even though the Munc13-1 and PSD-95 contents of individual synapses changed considerably over 15-22 h, Munc13-1/PSD-95 ratios, which varied over a fourfold range, were well conserved over these durations. These findings indicate that the "stoichiometries" of presynaptic and postsynaptic molecules can genuinely differ among synapses and that synapses can maintain their specific stoichiometries even in face of extensive presynaptic and postsynaptic remodeling.
突触会在数分钟、数小时和数天的时间尺度上发生大量的活动依赖性和非依赖性重塑。可以推测，突触前特性的变化应该与突触后特性的相应变化相匹配，反之亦然。无论在何处测量，突触前和突触后分子特性往往都相关，但这些相关性往往并不完美，这引发了关于这种不匹配的起源的问题：这些是异步重塑过程的“单一快照”分析的结果吗？或者，这是否表明突触在其突触前和突触后分子含量的“化学计量”上确实存在差异？如果是这样，这些“化学计量”是否随着时间的推移而保持不变？为了解决这些问题，我们在培养的皮质小鼠神经元网络中跟踪了突触前活性区分子 Munc13-1 和突触后分子 PSD-95 的匹配动力学。我们发现，突触前和突触后重塑通常高度相关，但这种相关性的程度变化很大，在一些突触中观察到相关性很小甚至为负。没有证据表明一个隔室的重塑总是先于另一个隔室的重塑。有趣的是，尽管单个突触的 Munc13-1 和 PSD-95 含量在 15-22 小时内发生了很大变化，但 Munc13-1/PSD-95 比值在四倍范围内变化，在这些时间内仍能很好地保持。这些发现表明，突触前和突触后分子的“化学计量”确实可以在不同的突触之间存在差异，并且即使在广泛的突触前和突触后重塑的情况下，突触也可以维持其特定的化学计量。
