Postsynaptic signaling during plasticity of dendritic spines

Abstract

Dendritic spines, small bulbous postsynaptic compartments emanating from neuronal dendrites, have been thought to serve as basic units of memory storage. Despite their small size (~0.1 femtoliter), thousands of species of proteins exist in the spine, including receptors, channels, scaffolding proteins and signaling enzymes. Biochemical signaling mediated by these molecules leads to morphological and functional plasticity of dendritic spines, and ultimately learning and memory in the brain. Here, we review new insights into the mechanisms underlying spine plasticity brought about by recent advances in imaging techniques to monitor molecular events in single dendritic spines. The activity of each protein displays a specific spatiotemporal pattern, coordinating downstream events at different microdomains to change the function and morphology of dendritic spines.

Paradoxical signaling regulates structural plasticity in dendritic spines

“…We further linked the Rhoactivity to myosin activity and assumed that spine volume increase was proportional to the generation of new actin barbed ends and that spine volume decrease was proportional to the myosin activity. The net result is spine volume increase and decrease that mimic the experimentally observed behavior (10,11,16).…”

“…These targets include the small GTPasesRho and Cdc42, which in turn, initiate phosphorylation cascades. The effects of Rho are localized to the stimulated spine, whereas Cdc42 phosphorylates targets in adjacent spines to facilitate later stages of LTP (16). Phosphorylated CaMKII has a limited halflife, because calcium calmodulin also activates protein phosphatase 1 (PP1) that dephosphorylates CaMKII, albeit with a slower timescale (21).…”

“…Although the temporal response of the spine volume change and the associated molecular events are well-documented (11,16,28), the dynamics of these processes has not been linked. Computational models can provide insight into the nonlinear molecular interactions, identify network motifs, and also, generate experimentally testable predictions.…”

“…The experimental data were extracted from figure 1D in the work by Murakoshi et al (16) using the digitize package in the statistical software R. Complete details of the digitize package and how to use it are provided in ref. 40.…”

“…In these studies, the simple idea that the same component can both activate and inhibit a response, resulting in robustness, was applied to many different systems. Here, we consider the same design principle for the dynamics of the dendritic spine and apply it to the core signaling network that regulates early LTP (16).…”