The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity

Abstract

The ability to form long-lasting memories is critical to survival and thus is highly conserved across the animal kingdom. By virtue of its complexity, this same ability is vulnerable to disruption by a wide variety of neuronal traumas and pathologies. To identify effective therapies with which to treat memory disorders, it is critical to have a clear understanding of the cellular and molecular mechanisms which subserve normal learning and memory. A significant challenge to achieving this level of understanding is posed by the wide range of distinct temporal and spatial profiles of molecular signaling induced by learning-related stimuli. In this review we propose that a useful framework within which to address this challenge is to view the molecular foundation of long-lasting plasticity as composed of unique spatial and temporal molecular networks that mediate signaling both within neurons (such as via kinase signaling) as well as between neurons (such as via growth factor signaling). We propose that evaluating how cells integrate and interpret these concurrent and interacting molecular networks has the potential to significantly advance our understanding of the mechanisms underlying learning and memory formation.

How the epigenome integrates information and reshapes the synapse

“…For example, integrins help to link actin filament bundles to the plasma membrane and the extracellular matrix 164 . Newly synthesized proteins are required to further reconstruct the cytoskeleton and thus to consolidate and maintain the potentiation of synapses 23,147,159,[165][166][167][168][169][170][171] .…”

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

“…Synapses can also be weakened (long-term depression, LTD). These mechanisms contribute to memory formation, and their contribution depends on the type of learning and the brain region involved (Ito et al 2014;Jörntell 2017;Mirisis et al 2016;Nabavi et al 2014;Whitlock 2006). Roles for LTD have been investigated in, for example, cerebellar motor learning (Ito et al 2014;Jörntell 2017).…”

The ELAV family of RNA-binding proteins in synaptic plasticity and long-term memory

“…Noting the critical involvement of PKC and p38 MAPK in ELAV activation, it is important to understand the role that these kinases play in learning and memory formation. Several comprehensive reviews exploring the role of these and other kinases in the induction of LTM and its underlying synaptic plasticity have been previously published (Kandel, 2001(Kandel, , 2012Mirisis et al, 2016;Sossin, 2007).…”

“…The C/EBP family of transcription factors (consisting of 6 isoforms) are immediate early genes downstream of CREB (Alberini, 2009;Alberini et al, 1994;Kandel, 2012;Mirisis et al, 2016). The expression, translation, and downstream function of the IEG and transcription factor C/EBP is an evolutionarily conserved mechanism critical for the formation of LTM from mollusks to mammals (Alberini et al, 1994;Taubenfeld et al, 2001).…”