Yang Yunlei, Wang Xiao-bin, Frerking Matthew, Zhou Qiang
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Neurosci. 2008 May 28;28(22):5740-51. doi: 10.1523/JNEUROSCI.3998-07.2008.
Stable expression of long-term synaptic plasticity is critical for the developmental refinement of neural circuits and for some forms of learning and memory. Although structural remodeling of dendritic spines is associated with the stable expression of long-term potentiation (LTP), the relationship between structural and physiological plasticity remains unclear. To define whether these two processes are related or distinct, we simultaneously monitored EPSPs and dendritic spines, using combined patch-clamp recording and two-photon time-lapse imaging in the same CA1 pyramidal neurons in acute hippocampal slices. We found that theta burst stimulation paired with postsynaptic spiking, which reliably induced LTP, also induced a rapid and persistent expansion of dendritic spines. Like LTP, this expansion was NMDA receptor dependent. Spine expansion occurred even when LTP was inhibited by postsynaptic inhibition of exocytosis or PKA (protein kinase A); however, under these conditions, the spine expansion was unstable and collapsed spontaneously. Furthermore, similar changes in LTP and spine expansion were observed when hippocampal neurons were treated with protein synthesis inhibitors. Like LTP, spine expansion was reversed by low-frequency stimulation (LFS) via a phosphatase-dependent mechanism, but only if the LFS was applied in a critical time window after induction. These results indicate that the initial expression of LTP and spine expansion is dissociable, but there is a high degree of mechanistic overlap between the stabilization of structural plasticity and LTP.
长期突触可塑性的稳定表达对于神经回路的发育完善以及某些形式的学习和记忆至关重要。尽管树突棘的结构重塑与长时程增强（LTP）的稳定表达相关，但结构可塑性与生理可塑性之间的关系仍不清楚。为了确定这两个过程是相关还是不同，我们在急性海马切片的同一CA1锥体神经元中，使用膜片钳记录和双光子延时成像相结合的方法，同时监测兴奋性突触后电位（EPSP）和树突棘。我们发现，与突触后放电配对的theta爆发刺激可靠地诱导了LTP，同时也诱导了树突棘的快速持续扩张。与LTP一样，这种扩张依赖于NMDA受体。即使通过突触后抑制胞吐作用或蛋白激酶A（PKA）抑制LTP，树突棘仍会发生扩张；然而，在这些条件下，树突棘的扩张是不稳定的，会自发塌陷。此外，当用蛋白质合成抑制剂处理海马神经元时，LTP和树突棘扩张也出现了类似的变化。与LTP一样，树突棘扩张可通过低频刺激（LFS）通过磷酸酶依赖性机制逆转，但前提是LFS要在诱导后的关键时间窗口内施加。这些结果表明，LTP的初始表达和树突棘扩张是可分离的，但结构可塑性的稳定与LTP之间存在高度的机制重叠。
