Deceased. Larry S. Benardo was associated with Departments of Physiology and Pharmacology and Department of Neurology.
Protein kinase Mζ enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors
Version of Record online: 6 FEB 2006
copyright © 2006 Wiley-Liss, Inc.
Volume 16, Issue 5, pages 443–452, 2006
How to Cite
Ling, D. S.F., Benardo, L. S. and Sacktor, T. C. (2006), Protein kinase Mζ enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors. Hippocampus, 16: 443–452. doi: 10.1002/hipo.20171
- Issue online: 21 APR 2006
- Version of Record online: 6 FEB 2006
- Manuscript Accepted: 9 DEC 2005
- New York City Speaker's Fund for Biomedical Research
- NIH. Grant Numbers: MH51677, NS038132
- NIH. Grant Numbers: MH057068, MH53576
- atypical PKC;
- long-term potentiation;
Protein kinase Mζ (PKMζ), a constitutively active, atypical PKC isoform, enhances synaptic strength during the maintenance of long-term potentiation (LTP). Here we examine the mechanism by which PKMζ increases synaptic transmission. Postsynaptic perfusion of PKMζ during whole-cell recordings of CA1 pyramidal cells strongly potentiated the amplitude of AMPA receptor (AMPAR)-mediated miniature EPSCs (mEPSCs). Nonstationary fluctuation analysis of events recorded before and after PKMζ enhancement showed that the kinase doubled the number of functional postsynaptic AMPAR channels. After sustained potentiation, application of a PKMζ inhibitor reversed the increase in functional channel number to basal levels, suggesting that persistent increase of PKMζ is required to maintain the postsynaptic localization of a mobile subpopulation of receptors. The kinase did not affect other sites of LTP expression, including presynaptic transmitter release, silent synapse conversion, or AMPAR unit conductance. Thus PKMζ functions specifically to establish and maintain long-term increases in active postsynaptic AMPAR number. © 2006 Wiley-Liss, Inc.