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The Journal of Neuroscience, June 4, 2008, 28(23):6000-6009; doi:10.1523/JNEUROSCI.0384-08.2008

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Cellular/Molecular
Recruitment of Calcium-Permeable AMPA Receptors during Synaptic Potentiation Is Regulated by CaM-Kinase I

Eric S. Guire, Michael C. Oh, Thomas R. Soderling, and Victor A. Derkach

Vollum Institute, Oregon Health & Sciences University, Portland, Oregon 97225

Correspondence should be addressed to Thomas R. Soderling, Vollum Institute L-474, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97225. Email: soderlit{at}ohsu.edu

Ca²⁺-permeable AMPA receptors (CP-AMPARs) at central glutamatergic synapses are of special interest because of their unique biophysical and signaling properties that contribute to synaptic plasticity and their roles in multiple neuropathologies. However, intracellular signaling pathways that recruit synaptic CP-AMPARs are unknown, and involvement of CP-AMPARs in hippocampal region CA1 synaptic plasticity is controversial. Here, we report that intracellular infusion of active CaM-kinase I (CaMKI) into cultured hippocampal neurons enhances miniature EPSC amplitude because of recruitment of CP-AMPARs, likely from an extrasynaptic pool. The ability of CaMKI, which regulates the actin cytoskeleton, to recruit synaptic CP-AMPARs was blocked by inhibiting actin polymerization with latrunculin A. CaMK regulation of CP-AMPARs was also confirmed in hippocampal slices. CA1 long-term potentiation (LTP) after theta bursts, but not high-frequency tetani, produced a rapid, transient expression of synaptic CP-AMPARs that facilitated LTP. This component of TBS LTP was blocked by inhibition of CaM-kinase kinase (CaMKK), the upstream activator of CaMKI. Our calculations show that adding CP-AMPARs numbering <5% of existing synaptic AMPARs is sufficient to account for the potentiation observed in LTP. Thus, synaptic expression of CP-AMPARs is a very efficient mechanism for rapid enhancement of synaptic strength that depends on CaMKK/CaMKI signaling, actin dynamics, and the pattern of synaptic activity used to induce CA1 LTP.

Key words: AMPA receptor; CaM-kinase; LTP; calcium; hippocampus; synaptic plasticity

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Received Jan. 28, 2008; revised April 9, 2008; accepted May 5, 2008.

Correspondence should be addressed to Thomas R. Soderling, Vollum Institute L-474, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97225. Email: soderlit{at}ohsu.edu

This article has been cited by other articles:

				J. Brill and J. R. Huguenard Sequential Changes in AMPA Receptor Targeting in the Developing Neocortical Excitatory Circuit J. Neurosci., December 17, 2008; 28(51): 13918 - 13928. [Abstract] [Full Text] [PDF]

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