Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Dendritic spines are small protrusive structures on dendritic surfaces, and function as postsynaptic compartments for excitatory synapses. Plasticity of spine structure is associated with many forms of long-term neuronal plasticity, learning and memory. Inside these small dendritic compartments, biochemical states and protein-protein interactions are dynamically modulated by synaptic activity, leading to the regulation of protein synthesis and reorganization of cytoskeletal architecture. This in turn causes plasticity of structure and function of the spine. Technical advances in monitoring molecular behaviors in single dendritic spines have revealed that each signaling pathway is differently regulated across multiple spatiotemporal domains. The spatial pattern of signaling activity expands from a single spine to the nearby dendritic area, dendritic branch and the nucleus, regulating different cellular events at each spatial scale. Temporally, biochemical events are typically triggered by short calcium pulses (approximately ten to one hundred milliseconds). However, these signals can then trigger activation of downstream protein cascades that can last from milliseconds to hours. Recent imaging studies provide many insights into the biochemical processes governing signaling events of molecular assemblies at different spatial localizations. Here, we highlight recent findings of signaling dynamics during synaptic plasticity and discuss their roles in long-term structural plasticity of dendritic spines.

INTRODUCTION

The dendritic spine is a small protrusive structure that typically houses a single excitatory postsynapse. The spine is made of a head (approximately zero point zero one to one femtoliters) and a narrow neck (approximately zero point one micrometer in diameter) that connects the head and dendritic surface. This structure spatially restricts electrical and biochemical access from the spine head to the dendritic shaft. This rather unusual structure is maintained by a network of actin cytoskeleton. The actin network also acts as a scaffold for stably positioning channels, cell adhesion proteins and sub-spine structure such as endosomes and postsynaptic densities.

While dendritic spines can be stable for months to years, which perhaps is important for stable function of neuronal circuits, structural plasticity of dendritic spines are known to be correlated with circuit plasticity during learning. Importantly, models of long-term synaptic plasticity such as long-term potentiation and long-term depression also are associated with long-term enlargement and shrinkage of dendritic spines, respectively. These forms of plasticity, termed structural long-term potentiation and structural long-term depression, are thus perhaps the basis of long-term circuit reorganization during learning and memory. Structural plasticity of dendritic spines is associated with molecular reorganization. For example, the actin cytoskeletal mesh, which maintains the spine structure, needs to be rearranged. In addition, postsynaptic density size and the number of glutamate receptors on the spine also changes.

Structural long-term potentiation is perhaps the most studied form of spine structural plasticity. It has been shown that plasticity has several temporal phases with distinct sensitivity to pharmacological and genetic perturbations. Immediately after induction (either by electrical stimulation or glutamate uncaging), spines undergo a rapid and large volume increase. This is called the transient phase, and the exact physiological role of this phase is unknown. The volume decreases over several minutes but stabilizes at a level higher than the original volume. This is called the sustained phase, and continues for more than an hour. This phase is associated with an increase in the postsynaptic sensitivity to glutamate. Depending on the conditions, the sustained phase can be protein-synthesis dependent.

The rapid and sustained structural remodeling of spines depends crucially on intracellular signaling networks to orchestrate posttranslational modifications and nascent protein synthesis. In this review article, we highlight recent findings demonstrating intracellular and extracellular molecular interactions regulating actin cytoskeleton as a structural basis of spine remodeling as well as implications of activity-dependent local translation for long-lasting synaptic plasticity.