  With memory encoding reliant on persistent changes in the properties of
synapses, a key question is how can memories be maintained from days to months
or a lifetime given molecular turnover? It is likely that positive feedback
loops are necessary to persistently maintain the strength of synapses that
participate in encoding. Such feedback may occur within signal-transduction
cascades and/or the regulation of translation, and it may occur within specific
subcellular compartments or within neuronal networks. Not surprisingly,
numerous positive feedback loops have been proposed. Some posited loops operate
at the level of biochemical signal transduction cascades, such as persistent
activation of calcium/calmodulin kinase II or protein kinase M. Another level
consists of feedback loops involving transcriptional, epigenetic and
translational pathways, and autocrine actions of growth factors such as BDNF.
Finally, at the neuronal network level, recurrent reactivation of cell
assemblies encoding memories is likely to be essential for late maintenance of
memory. These levels are not isolated, but linked by shared components of
feedback loops. Here, we review characteristics of some commonly discussed
feedback loops proposed to underlie the maintenance of memory and long-term
synaptic plasticity, assess evidence for and against their necessity, and
suggest experiments that could further delineate the dynamics of these feedback
loops. We also discuss crosstalk between proposed loops, and ways in which such
interaction can facilitate the rapidity and robustness of memory formation and
storage.
