Abstract
Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.
Highlights
Understanding the neurobiological basis of learning and memory is a major goal of modern neuroscience
Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time
The aim of this review is to identify the mechanism by which PKMζ maintains LTP and review the current evidence pertaining to the role of PKMζ in long-term memory maintenance
Summary
Understanding the neurobiological basis of learning and memory is a major goal of modern neuroscience. The main processes involved in memory formation are encoding, consolidation, storage, and retrieval (Brem et al 2013). Encoding is the acquisition of the memory in response to a perceived stimulus. Consolidation involves converting the newly acquired temporary and unstable memory, to a more stable and long-lasting memory. Storage can be classified into short-term memory, which is characterised by a small storage capacity and a rapid temporal decay, and longterm memory, which has a larger storage capacity and slower decay, allowing information to be retained for longer periods. Retrieval is described as the process of bringing information to the focus of attention (McElree 2006)
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