How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory

Abstract

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 Ca 2+ /calmodulin kinase II (CaMKII) or protein kinase M ζ. 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. Smolen et al. 3

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

“…The aIC has been implicated in self-referential processes, and our results further suggest learned aversive behavior to arise, at least in part, through changes in activity and connectivity of the region in relation to internal, subjective states (Critchley and Seth, 2012;Pais-Vieira et al, 2016). The aIC-to-BLA projection is necessary for CS-US association during CTA acquisition, and is subsequently reactivated to guide retrieval, likely consequent to brain-wide adaptations necessary for memory maintenance (Smolen et al, 2019). Future studies should dissect the role of aIC connectivity and distinct cell types in taste memory encoding, maintenance and retrieval more comprehensively.…”

Nicotine exposure and neuronal activity regulate Golgi membrane dispersal and distribution

“…A central question in neuroscience is how changes in postsynaptic activity in dendrites are integrated with other neural activity and result in functional plasticity over the shortterm, and structural plasticity over the long-term. The process of protein translation and its local control has long been implicated in long-term structural plasticity changes (Smolen, Baxter et al 2019). Our findings of previously undetected functional Golgi membranes throughout dendrites raises new possibilities of the existence of large numbers of LSUs that service postsynaptic sites.…”

Comparing Theories for the Maintenance of Late LTP and Long-Term Memory: Computational Analysis of the Roles of Kinase Feedback Pathways and Synaptic Reactivation

“…This model is simplified from those we have previously published (Smolen et al 2006(Smolen et al , 2014 in that it focuses on synapse-specific positive feedback loops. It does not represent gene induction and transcriptional or epigenetic positive feedback, although these have been hypothesized as permissive factors for maintaining memory (Smolen et al 2019;Zhang et al 2016). Smolen et al (2014).…”