Translating neuronal activity into dendrite elaboration: signaling to the nucleus

Growth and elaboration of neuronal processes is key to establishing neuronal connectivity critical for an optimally functioning nervous system. Neuronal activity clearly influences neuronal connectivity and does so via intracellular calcium signaling. A number of CaMKs and MAPKs convey the calcium signal initiated by neuronal activity. Several of these kinases interact with substrates in close proximity to the plasma membrane and alter dendrite structure locally via these local interactions. However, many calcium-activated kinases, such as Ras-MAPK and CaMKIV, target proteins in the nucleus, either by activating a downstream substrate that is a component of a signaling cascade or by directly acting within the nucleus. It is the activation of nuclear signaling and gene transcription that is thought to mediate global changes in dendrite complexity. The identification of calcium-sensitive transcription factors and transcriptional coactivators provides substantial evidence that gene transcription is a prevalent mechanism by which neuronal activity is translated into changes in dendrite complexity. The present review presents an overview of the role of neuronal activity in the development of neuronal dendrites, the signaling mechanisms that translate neuronal activity into gene transcription, and the transcribed effectors that regulate dendrite complexity.