Atypical PKCs in memory maintenance: the roles of feedback and redundancy
- 1Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas 77030, USA
- 2Department of Physiology, Pharmacology, Anesthesiology, and Neurology, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA
- Corresponding author: Harel.Shouval{at}uth.tmc.edu
Abstract
Memories that last a lifetime are thought to be stored, at least in part, as persistent enhancement of the strength of particular synapses. The synaptic mechanism of these persistent changes, late long-term potentiation (L-LTP), depends on the state and number of specific synaptic proteins. Synaptic proteins, however, have limited dwell times due to molecular turnover and diffusion, leading to a fundamental question: how can this transient molecular machinery store memories lasting a lifetime? Because the persistent changes in efficacy are synapse-specific, the underlying molecular mechanisms must to a degree reside locally in synapses. Extensive experimental evidence points to atypical protein kinase C (aPKC) isoforms as key components involved in memory maintenance. Furthermore, it is evident that establishing long-term memory requires new protein synthesis. However, a comprehensive model has not been developed describing how these components work to preserve synaptic efficacies over time. We propose a molecular model that can account for key empirical properties of L-LTP, including its protein synthesis dependence, dependence on aPKCs, and synapse-specificity. Simulations and empirical data suggest that either of the two aPKC subtypes in hippocampal neurons, PKMζ and PKCι/λ, can maintain L-LTP, making the system more robust. Given genetic compensation at the level of synthesis of these PKC subtypes as in knockout mice, this system is able to maintain L-LTP and memory when one of the pathways is eliminated.
Footnotes
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[Supplemental material is available for this article.]
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.038844.115.
- Received April 21, 2015.
- Accepted May 5, 2015.
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