Mapping Molecular Memory: Navigating the Cellular Pathways of Learning

Abstract

A consolidated map of the signalling pathways that function in the formation of short- and long-term cellular memory could be considered the ultimate means of defining the molecular basis of learning. Research has established that experience-dependent activation of these complex cellular cascades leads to many changes in the composition and functioning of a neuron's proteome, resulting in the modulation of its synaptic strength and structure. However, although generally accepted that synaptic plasticity is the mechanism whereby memories are stored in the brain, there is much controversy over whether the site of this neuronal memory expression is predominantly pre- or postsynaptic. Much of the early research into the neuromolecular mechanisms of memory performed using the model organism, the marine snail Aplysia, has focused on the associated presynaptic events. Recently however, postsynaptic mechanisms have been shown to contribute definitively to long term memory processes, and are in fact critical for persistent learning-induced synaptic changes. In this review, in which we aimed to integrate many of the early and recent advances concerning coordinated neuronal signaling in both the pre- and postsynaptic neurons, we have provided a detailed account of the diverse cellular events that lead to modifications in synaptic strength. Thus, a comprehensive synaptic model is presented that could explain a few of the shortcomings that arise when the presynaptic and postsynaptic changes are considered separately. Although it is clear that there is still much to be learnt and that the exact nature of many of the signalling cascades and their components are yet to be fully understood, this still incomplete but integrated illustrative map of the cellular pathways involved provides an overview which expands understanding of the neuromolecular mechanisms of learning and memory.

Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration

“…Therefore, we examined if there are activity-induced changes in the expression of known and newly identified EGR1 targets in the hippocampus and cortex of wild type mice. We chose a modification of the Morris Water Maze (MWM) paradigm that is widely used to study activity-dependent EGR1 mediated up-regulation of genes(D'Hooge and De Deyn, 2001; Fordyce et al, 1994; Guzowski et al, 2001; Owen and Brenner, 2012; Porte et al, 2008). As shown on Figure 3B, following a single-day MWM test, mRNA levels of the majority of genes chosen for validation in the hippocampus (including Egr1 ) were increased significantly as compared to caged controls, as were the positive controls Nab2 and Arc .…”

Dynamin 1 Is Required for Memory Formation

“…Memories are stored in the brain as short- and long-term changes in synaptic strength [16]. Because of this link, we next analyzed the effects of dynamin inhibition on synaptic functioning during high frequency stimulation, a type of sustained activity that is known to reinforce synapses.…”

Phosphodiesterase 11A (PDE11A), Enriched in Ventral Hippocampus Neurons, is Required for Consolidation of Social but not Nonsocial Memories in Mice

“…The fact that STM remains intact but LTM is impaired suggests that PDE11A KO mice retain their ability to learn social information and retrieve a social memory, but differ in their ability to transition that social memory from short-term to long-term status. Whereas STM largely relies on proteins that already exist at the synapse, transitioning a memory to long-term status requires de novo transcription and protein translation (c.f., ( Owen and Brenner, 2012 ; Rosenberg et al , 2014 )). In the VHIPP, PDE11A KO mice show a significant reduction in pS6–235/236, a commonly used biomarker of protein translation ( Figure 5b and c ).…”