Regulation of Dendritic Development by Neuronal Activity Yachi Chen, 1 Anirvan Ghosh 2 1 Department of Physiology and Neuroscience, Molecular Neurobiology Program, Skirball Institute, New York University, New York, New York 10016 2 Division of Biology, Neurobiology Section, University of California San Diego, La Jolla, California 92093-0366 Received 4 October 2004; accepted 2 November 2004 ABSTRACT: Proper development of dendrites is essential for the establishment of neuronal circuitry. The elaboration of the dendritic tree is a highly dynamic and regulated process, which involves the formation of new branches as well as the maintenance or elimination of pre-existing branches. This review describes recent advances in our understanding of the molecular mechanisms of activity-dependent dendritic development. Neuronal activity triggers calcium-medi- ated signaling events that affect the structural com- ponents of dendrites and adhesion molecules. These calcium-induced signaling pathways also target nuclear transcription factors thereby controlling expression of genes required for dendritic development. Thus, a coordinated response to calcium-regulated signaling pathways mediates activity-dependent dendritic devel- opment. ' 2005 Wiley Periodicals, Inc. J Neurobiol 64: 4–10, 2005 Keywords: dendrite; development; calcium Neurons extend dendrites to receive and integrate information from a vast number of synaptic inputs. The specific branching pattern or morphology of den- drites determines not only the number and type of synaptic contacts but also influences the back propa- gation of action potentials. Because dendritic morphol- ogy plays such a critical role in synaptic integration and information processing, it is important to under- stand how the development of dendrites is regulated. Different types of neurons in the central nervous system exhibit different dendritic morphologies. This type-specific morphology appears to be specified by genetic programs (Jan and Jan, 2003). These intrinsic programs act in concert with extracellular signals to specify the mature dendritic arbor. The extracellular influences include various protein factors as well as neuronal activity (Wong and Ghosh, 2002; Miller and Kaplan, 2003). The effects of neuronal activity on dendritic development are mediated by intracellular calcium signals, and recent studies indicate that cal- cium-induced signaling events have both cytoplasmic and nuclear targets. In this review, we will focus on advances in our understanding of the regulation of dendritic arbor development by neuronal activity. Specifically, we will discuss the calcium-dependent signaling events that affect the dendritic cytoskeleton and gene expression. Studies supporting a role of neu- ronal activity in dendritic spine development have been reviewed elsewhere (Nimchinsky et al., 2002; Yuste and Bonhoeffer, 2004). REGULATION OF DENDRITIC BRANCH STABILITY BY NEURONAL ACTIVITY The development of dendritic arbors is a highly dynamic process. As evident by time-lapse imaging studies using different experimental models, it involves both the addition of new branches, as well Correspondence to: A. Ghosh (aghosh@ucsd.edu). ' 2005 Wiley Periodicals, Inc. Published online in Wiley InterScience (www.interscience.wiley. com). DOI 10.1002/neu.20150 4