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Memory maintenance by PKMζ — an evolutionary perspective

Overview of attention for article published in Molecular Brain, September 2012
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217 Mendeley
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Title
Memory maintenance by PKMζ — an evolutionary perspective
Published in
Molecular Brain, September 2012
DOI 10.1186/1756-6606-5-31
Pubmed ID
Authors

Todd Charlton Sacktor

Abstract

Long-term memory is believed to be maintained by persistent modifications of synaptic transmission within the neural circuits that mediate behavior. Thus, long-term potentiation (LTP) is widely studied as a potential physiological basis for the persistent enhancement of synaptic strength that might sustain memory. Whereas the molecular mechanisms that initially induce LTP have been extensively characterized, the mechanisms that persistently maintain the potentiation have not. Recently, however, a candidate molecular mechanism linking the maintenance of LTP and the storage of long-term memory has been identified. The persistent activity of the autonomously active, atypical protein kinase C (aPKC) isoform, PKMζ, is both necessary and sufficient for maintaining LTP. Furthermore, blocking PKMζ activity by pharmacological or dominant negative inhibitors disrupts previously stored long-term memories in a variety of neural circuits, including spatial and trace memories in the hippocampus, aversive memories in the basolateral amygdala, appetitive memories in the nucleus accumbens, habit memory in the dorsal lateral striatum, and elementary associations, extinction, and skilled sensorimotor memories in the neocortex. During LTP and memory formation, PKMζ is synthesized de novo as a constitutively active kinase. This molecular mechanism for memory storage is evolutionarily conserved. PKMζ formation through new protein synthesis likely originated in early vertebrates ~500 million years ago during the Cambrian period. Other mechanisms for forming persistently active PKM from aPKC are found in invertebrates, and inhibiting this atypical PKM disrupts long-term memory in the invertebrate model systems Drosophila melanogaster and Aplysia californica. Conversely, overexpressing PKMζ enhances memory in flies and rodents. PKMζ persistently enhances synaptic strength by maintaining increased numbers of AMPA receptors at postsynaptic sites, a mechanism that might have evolved from the general function of aPKC in trafficking membrane proteins to the apical compartment of polarized cells. This mechanism of memory may have had adaptive advantages because it is both stable and reversible, as demonstrated by the downregulation of experience-dependent, long-term increases in PKMζ after extinction and reconsolidation blockade that attenuate learned behavior. Thus, PKMζ, the "working end" of LTP, is a component of an evolutionarily conserved molecular mechanism for the persistent, yet flexible storage of long-term memory.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 217 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 6 3%
France 3 1%
United Kingdom 2 <1%
Russia 2 <1%
Norway 1 <1%
Brazil 1 <1%
Sweden 1 <1%
Germany 1 <1%
Canada 1 <1%
Other 3 1%
Unknown 196 90%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 45 21%
Student > Master 35 16%
Student > Bachelor 27 12%
Researcher 23 11%
Professor 15 7%
Other 45 21%
Unknown 27 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 65 30%
Neuroscience 45 21%
Psychology 28 13%
Medicine and Dentistry 16 7%
Biochemistry, Genetics and Molecular Biology 12 6%
Other 20 9%
Unknown 31 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 August 2014.
All research outputs
#16,721,717
of 25,374,647 outputs
Outputs from Molecular Brain
#678
of 1,198 outputs
Outputs of similar age
#120,936
of 188,973 outputs
Outputs of similar age from Molecular Brain
#8
of 14 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,198 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.9. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 188,973 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.