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The Journal of Neuroscience, May 28, 2008, 28(22):5740-5751; doi:10.1523/JNEUROSCI.3998-07.2008

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Cellular/Molecular
Spine Expansion and Stabilization Associated with Long-Term Potentiation

Yunlei Yang,^1 * Xiao-bin Wang,^1 * Matthew Frerking,² and Qiang Zhou¹

¹Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, and ²Neurological Science Institute, Oregon Health & Science University, Portland, Oregon 97006

Correspondence should be addressed to Dr. Qiang Zhou, Department of Neurology, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1137, New York, NY 10029. Email: qiang.zhou{at}mssm.edu

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.

Key words: LTP; dendritic spines; actin; AMPA receptors; depotentiation; two-photon imaging

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Received June 19, 2007; revised Feb. 14, 2008; accepted March 5, 2008.

Correspondence should be addressed to Dr. Qiang Zhou, Department of Neurology, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1137, New York, NY 10029. Email: qiang.zhou{at}mssm.edu

This article has been cited by other articles:

				Y. Yang, X.-b. Wang, M. Frerking, and Q. Zhou Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation PNAS, August 12, 2008; 105(32): 11388 - 11393. [Abstract] [Full Text] [PDF]

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